bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P024: Blood Pressure Levels, Aggressiveness of Antihypertensive Therapy, and Prevalence of Left Ventricular Hypertrophy
Authors: Lakkur Sindhu , Soliman Sayed , Oparil Suzanne , Judd Suzanne , Howard George 
Published: July 2021

A major cause of left ventricular hypertrophy (LVH) is an excessive hemodynamic load, making LVH more common among people with hypertension. Clinical trials of antihypertensive medication have found that treatment reduces left ventricular mass among those with hypertension, but little is known about the prevalence of LVH in the general population that are taking, and not taking, antihypertensive medication. We examined the cross-sectional association between blood pressure control and LVH among 28,106 participants in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, to test the hypotheses that: 1) within strata of blood pressure control, LVH will be more prevalent in those requiring more intensive treatment, and 2) that within strata of intensiveness of blood pressure treatment, that LVH will be more prevalent at higher blood pressure levels.
The REGARDS study enrolled black and white participants, aged 45 and older, from 2003-2007. Systolic blood pressure was defined as normal (<120 mmHg), prehypertension (120 mmHg - 139 mmHg), stage 1 (140 mmHg - 159 mmHg), and stage 2 hypertension (>160 mmHg). Classes of antihypertensive medications at baseline were defined as 0, 1, 2, or 3 or more. LVH by electrocardiogram was detected in 2,803 participants. Multivariable-adjusted odds ratios (ORs) for LVH and 95% confidence intervals (CIs) were calculated using logistic regression models.
The ORs (95% CIs) for each additional medication class were 1.31 (1.20-1.43) for normal blood pressure, 1.21 (1.14-1.27) for prehypertension, 1.07 (0.98-1.16) for stage 1, and 1.02 (0.88-1.17) for stage 2. The ORs (95% CIs) for each additional increase in blood pressure category were 1.57 (1.41-1.75) for no medications, 1.47 (1.33-1.63) for 1, 1.30 (1.18-1.43) for 2, and 1.21 (1.10-1.34) for 3 medications.
We observed that successful blood pressure control by medication is still associated with elevated odds of LVH compared to untreated normotensive participants, emphasizing the importance of hypertension prevention.
Abstract P157: Serum Vitamin D is Not Associated With Risk of Incident Diabetes in African Americans: The Jackson Heart Study
Authors: Harman Jane L , Chen Haiying , Sachs Michael C , Hairston Kristin G , Golden Sherita H , Joseph Joshua J , Bertoni Alain G 
Published: July 2021

A recent meta-analysis of cohort studies with participants primarily of European ancestry, concluded that the risk of incident diabetes was inversely proportional to serum 25-hydroxy-vitamin D levels (25-OH-D). African Americans have lower levels of vitamin D than European Americans. But, lower levels of vitamin D do not seem to carry the same risk for low bone density or vascular calcification for African Americans. We sought to test the hypothesis that low vitamin D elevates the risk of diabetes in African Americans.
During 2001-5, 5301 African American adults in Jackson, MS, were examined and blood samples drawn; mean age was 55±13. Serum 25-OH-D2 and 25-OH-D3 were measured from stored frozen serum; mean total 25-OH-D (25-OH-D2 plus 25-OH-D3) =14.5±6.7ng/ml. A seasonal pattern was evident for 25-OH-D3 but not for 25-OH-D2 levels. A cosinor model adjusted for seasonality of 25-OH-D3; mean annualized concentrations and seasonal amplitude were significantly higher for men and for persons of normal BMI compared to overweight or obese persons. Total 25-OH-D, as the sum of predicted annualized mean 25-OH-D3 and measured 25-OH-D2, was used in subsequent analysis.
The analysis evaluated 3363 participants after exclusions for missing serum vitamin D (n=141), prevalent diabetes (n=1152), incomplete ascertainment of diabetes (n=62), or no follow-up (n=725). During a mean follow-up of 7.1 years, there were 584 new cases of diabetes. Using a Cox Proportional Hazards model controlling for age and sex, the risk of incident diabetes was significantly and inversely associated with total serum 25-OH-D; after adding BMI to the model, 25-OH-D was not significantly associated with risk of diabetes (Table 1). Physical activity, smoking, and alcohol use did not predict incident diabetes in any model.
In conclusion, we found that in this cohort of African-Americans, with low mean 25-OH-D and a relatively narrow range of 25-OH-D, the risk of incident diabetes was not associated with serum 25-OH-D levels after controlling for sex, age, and BMI.
Abstract P392: Exome Sequencing From Extreme Responders to Aspirin Identifies a Novel Variant Associated With Platelet Aggregation
Authors: Backman Joshua , Ning Baitang , Lou Wensheng , Perry James , Shi Leming , Shuldiner Alan , Yerges-Armstrong Laura 
Published: July 2021

Platelet dysregulation is integral in the formation of thrombi, and abnormal thrombus formation may ultimately lead to myocardial infarctions or stroke. Thus platelets, and more specifically platelet activation and aggregation pathways, are prime targets for intervention. Aspirin or Dual Anti-Platelet Therapy with Aspirin and Clopidogrel (DAPT) is often prescribed for primary and secondary prevention of cardiovascular events, however, these treatments often fail to significantly reduce thrombi formation in a large percentage of patients. Recent studies indicate that platelet aggregation response is highly heritable. To identify novel variants that may have a significant impact on platelet aggregation, we conducted whole exome sequencing and follow-up DNA genotyping on a cohort of Old Order Amish subjects with well tracked family histories and platelet response phenotypes. 30 individuals from the extremes of collagen-mediated platelet aggregation response to aspirin were analyzed to identify variants enriched in the high or low responders. One of the top hits in this analysis was rs17834991, a synonymous variant in the SVIL gene enriched in the high aspirin response group that has not previously been associated with platelet aggregation. The SVIL gene encodes two proteins: a muscle-specific isoform, Archvillin, as well as a ubiquitous form, Supervillin, that is expressed in platelets. In a previous study, mutations in SVIL were found to be associated with inhibition of platelet aggregation under shear stress conditions.
To follow up our initial findings, we genotyped rs17834991 in 851 healthy Amish individuals with platelet aggregation measured before and after a two-week 81mg/day Aspirin intervention from our HAPI dataset. An additional 661 Amish subjects with platelet aggregation measured before and after 1 week of Clopidogrel treatment, and following one 81mg dose of Aspirin plus Clopidogrel from our PAPI cohort were genotyped. We then conducted a multivariable linear regression controlling for age, sex, BMI, and two known effectors of platelet aggregation: CYP2C19*2 and rs12041331. Our findings indicate that rs17834991 is significantly associated with change in collagen-mediated aggregation with aspirin in whole blood (p=4.8x10-4), as well as lag time until maximum aggregation with collagen post aspirin (1.6x10-3) in whole blood. Additional associations were identified with collagen mediated aggregation in PRP, the strongest being change in lag time in post DAPT vs post Clopidogrel-alone samples (6.59x10-5). These findings suggest that SVIL variant rs17834991 significantly alters platelet response following Aspirin and DAPT treatment. Taken with previous findings, SVIL may not only play a role in platelet function but may also impact anti-platelet intervention. Further studies are warranted to elucidate its potential impact on cardiovascular disease.
Abstract 171: A Mitral Regurgitation May be an Early Diagnostic Clue to Kawasaki Disease in Young Infants with Atypical Presentations
Authors: Oh Jin-Hee , Kim Ji Hoon , Lee Ji Eun , Kwon Hyo Jin , Lee Jae Young , Lee Soon Ju , Han Ji Whan , Lee Kyung Yil , Koh Dae Kyun 
Published: July 2021

Background:
Very young infants with Kawasaki disease (KD) often present with atypical features that render diagnosis difficult and the incidence of coronary complications high. Picking up clues at early phase of KD can be critical. Herein we present 3 cases of KD in very young infants who showed mitral regurgitation (MR) around the 7th day from the onset of fever. They received IVIG around 7th fever day. However, the advice for short-term follow up echocardiography (ECHO) was neglected as clinical course thereafter were so unusual. Giant coronary aneurysms developed in all the patients later.

Case 1: A 31-day-old infant got admission care for sepsis. ECHO at the 7th day from the onset of fever showed trivial MR and the patient received IVIG. Follow up ECHO was recommended, but was not conducted as clinical course was ambiguous for KD thereafter. Being treated with steroids due to skin rash and eosinophilia that masked patient’s fever, the infant reappeared to hospital with cardiogenic shock 10 days later. ECHO revealed giant aneurysms in the right coronary artery (RCA) and CT angiography for pulsating axillary masses revealed axillary aneurysms.
Case 2; A 67-day-old infant was admitted with fever and persistent thrombodytopenia. ECHO done at the 5th day from the onset of fever due to red lips showed non-specific findings. Follow up ECHO at the 7th fever day showed newly developed MR. IVIG and steroids was added on for persistent fever, but severe leukocytosis ensued and clinical course was also ambiguous for KD. Defervescence was achieved with infliximab. The infant showed coronary aneurysms.
Case 3; A 80-day-old infant was admitted with fever and seizure, and treated for sepsis. On the 6th day from the onset of fever, MR was shown on ECHO and the patient received IVIG and steroids. However, fever and severe anemia, left shift of leukocytes, and severe thrombocytopenia persisted for two weeks. Giant coronary aneurysms, as large as the ascending aorta, developed in the RCA. Pulsatile masses identified in the axilla were found to be large aneurysms on CT angiography.

Conclusion:
A newly developed MR, even trivial, around the 7th day from the onset of fever may be a clue to the diagnosis of KD and short term follow up ECHO is recommended for ongoing febrile infants younger than 3 months.
Abstract 180: Coronary Artery Aneurysms Identified At School Cardiac Screening
Authors: Yoshimoto Hironaga , Suda Kenji , Kishimoto Shintaro , Kudo Yoshiyuki , Matsuishi Toyojiro , Yatsunami Koichi 
Published: July 2021

Because most significant complication of Kawasaki disease (KD) is coronary aneurysms, echocardiography is an indispensable part of clinical practice and quality control of echocardiography is mandatory. On the other hand, Japanese government has enforced a law of regular school cardiac screening (SCS) at 1st, 7th, and 10th grader in 1995 and all patients with a history of KD were screened for coronary artery lesion. In this study we report 2 patients with coronary aneurysms picked up by SCS.
Case1: A 6-year-old boy was diagnosed with KD at 3 year old and received immunoglobulin (2g/kg/day). His condition improved within 8 days of illness and echocardiographic finding of coronary artery was “normal” in acute phase and at 1and 3 months after the onset of KD. Since then he did not visit clinic for follow-up. At 1st grader SCS, he was diagnosed as having giant coronary artery aneurysms by echocardiography. Indeed coronary angiography revealed sequential coronary aneurysms of 10.8 mm and 12.3 mm in diameter at segment 6 and 5 with a 99% stenosis in between them. Because of signs of coronary ischemia on myocardial perfusion scan, he underwent percutaneous coronary interventions and coronary artery bypass graft surgery later.
Case2: A 9-year-old boy was diagnosed with juvenile idiopathic arthritis and his fever continued 10 days. He underwent echocardiography at 9 days of illness but coronary artery lesions were not found. At 7th grader SCS, he was diagnosed as having coronary artery aneurysms by echocardiography. Coronary angiography revealed coronary artery aneurysms of 6.1mm and 6.1 mm in diameter at segment 1 and segment 6. Since then he has been placed on oral aspirin.
These 2 cases highlight the issue concerning timing and quality of echocardiography and importance of SCS in detecting patients with coronary undiagnosed aneurysms.
Abstract 70: Trial of Ulinastatin treatment for murine model of Kawasaki Desease
Authors: Tsujita Yuki , Kawamura Yoichi , Kanai Takashi , Takeshita Seiichiro , Nonoyama Shigeaki 
Published: July 2021

Recently, we reported that the initial Ulinastatin (UTI) therapy combined with intravenous immunoglobulin (IVIG) reduced the proportion of patients with Kawasaki disease requiring additional rescue treatment and the occurrence of coronary artery lesions as compared with IVIG alone (Circulation. 2011;124(25):2822-2828.). However, there have been no reports that histologically examined the therapeutic effects of UTI., In the present study, to investigate the histological efficacy of UTI, we administered UTI in a vasculitis murine model, resembling Kawasaki disease
Four-week-old male mice DBA/2 were intraperitoneally administered Candida albicans water soluble extract (CAWS) for 5 days and were treated either with UTI, IVIG, or a combination of UTI and IVIG. Further, we examined the plasma levels of neutrophil elastase andcytokinesandevaluated histopathological features..
Neutrophil elastase, TNF-α, IL-6, IP-10, and MIG significantly increased in the CAWS-treated mice. Large amount of elastase-positive neutrophils infiltrated in the coronary tissue. In addition, the infiltration of elastase-positive neutrophils was reduced in the pathological tissue of the UTI treatment group.
Neutrophil elastase is strongly involved in the destruction of the elastic plate and smooth muscle layer. There is a possibility that destruction of the vascular structures can be suppressed by decreasing the elastase-positive neutrophils infiltration in the UTI treatment group.
Abstract 12630: Cardiovascular Safety of Liraglutide: Pooled Analysis of Major Adverse Cardiovascular Events across Weight Management and Type 2 Diabetes Development Programs
Authors: Caterson Ian D , Bain Stephen C , Gross Jorge , House John , Salisbury Adam C , Baeres Florian M , Donsmark Morten , Marso Steven P 
Published: July 2021

The cardiovascular safety of liraglutide in individuals with overweight/obesity and those with type 2 diabetes (T2D) is unknown. A meta-analysis of five phase II/III liraglutide (dose up to 3.0 mg) weight management (WM) trials was performed. Additional sensitivity meta-analyses of 21 liraglutide T2D trials (dose up to 1.8 mg) and a pre-specified pooled analysis of all WM and T2D trials (27 trials; WM+T2D) were also conducted.
The primary endpoint was first occurrence of adjudicated major adverse cardiovascular events (MACE) (non-fatal myocardial infarction, non-fatal stroke or cardiovascular death) with liraglutide (any dose) or pooled total comparator (placebo, active) and analysis was using a Cox proportional hazards model stratified by trial. Prospective adjudication (blinded, independent) was implemented in three of the WM trials; post-hoc adjudication was conducted for all other trials. For WM trials, the observation period was from the first drug dose to the last drug dose plus a 30-day follow-up; for the SCALE Obesity and Prediabetes trial, data to October 1, 2014 were included.

For WM trials (liraglutide: n=3,872; comparator: n=2,036), baseline characteristics were: 71% women; history of CV disease, 9%; mean age, 47 yrs; mean BMI, 38 kg/m
2
. For T2D trials (liraglutide: n=5,511; comparator: n=2,748): 43% women; history of CV disease, 13%; mean age, 56 yrs; mean BMI, 30 kg/m
2
.

In WM trials (n=20 events), the hazard ratio (HR) [95% confidence interval (CI)] for MACE (liraglutide/comparator) was 0.45 [0.18; 1.10] (Figure 1A). In T2D trials (n=49 events), the HR was 0.64 [0.35, 1.15] (Figure 1A). For the WM+T2D analysis (n=69 events), the HR was 0.57 [0.35, 0.94] (Figure 1B).
In a pooled analysis of WM+T2D trials, MACE was significantly lower in patients treated with liraglutide. The dedicated cardiovascular outcomes trial, LEADER, will provide further insights into the cardiovascular safety of liraglutide.
Abstract 12635: Nationwide Long-term Follow-up of Pulmonary Atresia With Ventricular Septal Defect
Authors: Kaskinen Anu , Happonen Juha-Matti , Mattila Ilkka P , Pitkänen Olli M 
Published: July 2021

Introduction:
The naturally poor survival of pulmonary atresia with ventricular septal defect (PA+VSD) has improved due to evolved perioperative and surgical treatment. Studies including PA+VSD patients, both with and without major aortopulmonary collateral arteries (MAPCAs), with extensive follow-up are scarce. This nationwide study aimed to investigate survival and surgical treatment in PA+VSD patients with and without MAPCAs.

Methods:
Study comprised 109 PA+VSD patients born in Finland between 1970 and 2007. We reviewed retrospectively medical records and operative reports through December 2011, as well as first available angiograms and preoperative angiograms prior to repair attempt.

Results:
The median follow-up time for the total study population, including also patients who died during the follow-up, was 11.4 years (IQR 0.8 - 21.1). The incidence of PA+VSD, which could be determined reliably from 1995 to 2007, was 6.1 per 100 000 live births.

Although the patients with (n = 43) or without MAPCAs (n = 66) showed no difference in survival (p = 0.74), the patients without MAPCAs had better probability to achieve repair (64% vs. 28%, p < 0.0001). The bigger size of true central pulmonary arteries assessed by McGoon index at first angiogram [HR 0.66 (CI95% 0.49 - 0.88) per 0.5 McGoon index units, p = 0.006] and achievement of repair [HR 0.07 (CI95% 0.03 - 0.17), p < 0.0001] improved the overall survival.
After successful repair survival was 93% at 1 year and 91% from 2 years on. Palliated patients, instead, had survival at 1, 5, 10, and 20 years of age of 55%, 42%, 34%, and 20% respectively. However, patients with right ventricle - pulmonary artery connection and septal fenestration had better survival than rest of the palliated patients (p = 0.001). Palliation with a systemic-pulmonary artery shunt increased McGoon index by 41% (p < 0.0001).

Conclusions:
The patients with MAPCAs had higher risk to remain palliated than patients without, although their survival was similar. Survival of PA+VSD was influenced by the initial size of true central pulmonary arteries and whether repair was achieved. Although palliative procedures may not improve the final outcome of PA+VSD, palliative surgery may have a role in its treatment.
Abstract 13929: Pulmonary Artery Diameter Index Predicts the Complications of Balloon Pulmonary Angioplasty
Authors: Sugimoto Koichi , Nakazato Kazuhiko , Yoshihisa Akiomi , Sakamoto Nobuo , Yamaki Takayoshi , Kunii Hiroyuki , Takeishi Yasuchika 
Published: July 2021

Backgrounds:
Balloon pulmonary angioplasty (BPA) has been an attractive strategy as a new treatment for peripheral type chronic thromboembolic pulmonary hypertension (CTEPH). However, BPA occasionally causes fatal complications such as hemorrhagic pulmonary edema, and asymptomatic mild lung injury detected on computed tomography (CT) image is not rare. Pathogenesis of lung injury after BPA has been considered to be a direct vascular injury due to guide wire or balloon, cytokine release at the time of reperfusion, and vulnerability of peripheral pulmonary vascular wall. However, predictive factors of lung injury have not been established.

The pulmonary artery expansion of the central portion is frequently observed in patients with advanced pulmonary hypertension and the pulmonary artery diameter can be measured easily and accurately by CT.
Therefore, we focused on the pulmonary artery diameter and investigated the association between complications after BPA.

Methods:
The subject consisted of 16 CTEPH patients diagnosed by right heart catheterization and pulmonary arteriography who underwent BPA (2 males, 14 females, age 60.5 ± 11 years. Initial hemodynamic indices of study subjects were mean pulmonary artery pressure (mPAP) 48.8±12.8 mmHg, cardiac output (CO) 3.62±1.07 L/min, and pulmonary vascular resistance (PVR) 11.6±8.15 WoodUnits. Patients were divided into two groups: group N (no symptoms or signs of any complications, n=9) and group C (symptoms such as hemoptysis or lung infiltration on CT image without symptoms, n=7). We measured pulmonary artery diameter on CT at the transition from the main trunk to the right pulmonary artery and corrected by body surface area. We defined this as the pulmonary diameter index.

Results:
CO was lower in group C than in group N, but there was no difference in mPAP, PVR, BNP, and the use of pulmonary vasodilators between two groups. Pulmonary artery diameter index in group C was significantly higher than that in group N (21.95 ± 5.89 vs. 14.22 ± 2.41 mm/m
2
, P<0.01). ROC curve indicated 85.7% sensitivity and 88.9% specificity using cut-off value of 18.0 to predict the complications after BPA.

Conclusions:
Our study suggested that pulmonary artery diameter index would be a novel predictor of the complications after BPA.
Abstract 15187: Shear Stress-regulated Mir-27b Controls Pericyte Recruitment
in vitro
and
in vivo
and Contributes to Vessel Maturation
Authors: Demolli Shemsi , Doddaballapur Anuradha , Stark Konstantin , Boon Reinier A , Eckart Ankathrin , Korff Thomas , Hecker Markus , Manavski Yosif , Lucas Tina , Massberg Steffen , Devraj Kavi , Liebner Stefan , Kaluza David , Dimmeler Stefanie 
Published: July 2021

Vessel maturation involves recruitment of mural cells. Laminar shear stress is a major trigger for vessel maturation. However, the molecular mechanisms by which shear stress affects recruitment of pericytes are unclear. MicroRNAs are small non-coding RNAs, which post-transcriptionally control gene expression. Since shear stress regulates various miRs, we hypothesize that flow-induced miRs inhibit repulsive cues and facilitate mural cell coverage.
Laminar shear stress for 72h induces the up-regulation of miR-27b (2.8±0.24-fold vs static, p<0.05) in cultured endothelial cells (ECs) and in mouse femoral artery segments that were exposed to physiological shear stress ex vivo (1.5±0.14-fold vs no flow, p<0.05). Predicted targets for miR-27b include members of the semaphorin (SEMA) family (known to regulate repulsive signaling) and angiopoietin-2 (Ang2), which causes vessel destabilization. MiR-27b overexpression reduces SEMA6A (63.5±13.5%), SEMA6D (58±26%), and Ang2 (51.5±11%) expression.
To determine whether miR-27b controls pericyte recruitment, we tested the effect of endothelial miR-27b on adhesion of pericytes. Overexpression of miR-27b increased the adhesion of pericytes (p<0.05) and inhibition of miR-27b reduced pericyte adhesion in vitro (p<0.05). In an in vitro matrigel assay, overexpression of miR-27b increased pericyte coverage of endothelial cell tubes (155±45%, p<0.05), whereas inhibition of miR-27b reduced pericyte coverage (81±15%). In addition, overexpression of miR-27b in vitro increases barrier function (p<0.05) in endothelial cell-pericyte co-culture assays whereas inhibition of miR-27b decreases barrier function (p<0.05). Silencing of SEMA6A and SEMA6D rescued the reduced pericyte adhesion that is caused by miR-27 inhibition (p<0.05). Furthermore, inhibition of SEMA6D increases barrier function. In vivo inhibition of miR-27a/b significantly increased edema (p<0.05) in the uterus which was associated with a significantly reduced pericyte coverage of the vessels (p<0.05).
Taken together, our data demonstrate that shear stress regulate miR-27b, which targets Ang2 and semaphorins, thereby controlling pericyte adhesion and coverage in vitro and in vivo.