bluuebunny/crossref_metadata_2025_split huggingface dataset:
P6185Impact of coronary atherosclerotic plaque metrics on the correlation between on-site CT-FFR and invasive FFR
Authors: Bos Real L , Vilades D , Jimenez M , Altisent O , Rodriguez O , Alomar X , Ferrero A , Schuijf J , Carreras F , Leta R 
Published: October 2019

Abstract

Background
Developed in the last years, coronary computed tomography-derived fractional flow reserve (CT-FFR) has shown good correlation with invasive fractional flow reserve (FFR). However, little is known about the interaction of coronary atherosclerotic plaque characteristics in the correlation between CT-FFR and FFR.

Purpose
This study sought to determine the effect of main coronary atherosclerotic plaque metrics (APM) on the correlation between on-site CT-FFR and invasive FFR.

Methods
Patients referred for invasive coronary angiography (ICA) who accepted to undergo a CT-FFR study were prospectively included. We excluded patients with atrial fibrillation, chronic total occlusions, severe ventricular hypertrophy or previous coronary revascularization, and those with any contraindication for CT. On-site CT-FFR and APM were calculated for each coronary vessel. Continuous variables of APM were dichotomized as above and below the median and their interaction on the correlation between on-site CT-FFR and invasive FFR was assessed by multiple linear regression model.

Results
33 patients (90 vessels) were included. Mean age was 65±10 years, 88% were males, 60% had hypertension, 77% dyslipidaemia and 40% diabetes. The mean delay time between CTA and ICA of 21 days. The average analysis time of CT-FFR was 16±4 minutes. Overall, correlation between FFR and CT-FFR showed a Pearson's r coefficient of 0.77±0.06 and a standardized beta coefficient of 0.8 (p<0.001). The beta coefficients between CT-FFR and FFR did not change significantly after the interaction with different APM (p>0.05 for all) (see Table).
Standardized Beta coefficients for on-site CT-FFR with invasive FFR as a gold standard Below the median Above the median p value for interaction Total atheroma volume (TAV) (mm3) 0.66 0.93 0.071 Percent atheroma volume (PAV) (%) 1.00 0.69 0.063 Calcified atheroma plaque volume (%) 0.89 0.68 0.175 Remodeling index 0.94 0.71 0.129 Lesion length (LL) (mm) 0.67 0.89 0.158 Minimal lumen area (mm2) 0.73 0.71 0.955

Conclusions
There is a good correlation between on-site CT-FFR and invasive FFR, which is not affected by main atherosclerotic plaque characteristics.
P6194Therapeutic effect of nanoliposomal anti-PCSK9 vaccine on hypercholesterolemia and atherosclerosis in C57BL/6 mice
Authors: Momtazi-Borojeni A A , Jaafari M R , Banach M , Sahebkar A 
Published: October 2019

Abstract

Background
Proprotein convertase subtilisin/kexin 9 (PCSK9) promotes hypercholesterolemia through reducing protein level of liver low-density lipoprotein (LDL) receptor (LDLR). Currently, PCSK9 inhibition is known as an efficient lipid-lowering approach.

Purpose
Here, we constructed a liposomal anti-PCSK9 vaccine, and evaluated its therapeutic effects on dyslipidemia and atherosclerosis in atherosclerotic mice.

Methods
Liposomal anti-PCSK9 vaccine was prepared viaattaching immunogenic peptide, termed Immunogenic Fused PCSK9-Tetanus (IFPT), on the surface of nanoliposome carriers by using DSPE-PEG-Maleimide lipid (L-IFPT). The L-IFPT formulation was adsorbed to Alum adjuvant (L-IFPTA+) and administrated subcutaneously four times with a bi-weekly interval in hypercholesterolemic C57BL/6 mice. Plasma levels of anti-PCSK9 antibody, plasma concentration of PCSK9 protein, effect of anti-PCSK9 antibody on PCSK9-LDLR interaction, protein levels of liver LDLR, lipid profile, as well as atherosclerotic lesion size and severity were measured in the vaccinated hypercholesterolemic mice. To determine immune safety, Inflammatory response was measured by evaluating IFN-γ and IL-10 producing splenic cells using ELISpot assay.

Results
L-IFPTA+vaccine promoted the high IgG antibody response against PCSK9 peptide in the hypercholesterolemic mice. L-IFPTA+-induced antibodies targeted plasma PCSK9 and thereby decreased plasma consecration of PCSK9, which was associated with the reduced PCSK9-LDLR interaction and the increased liver levels of LDLR protein. Inhibitory effect of L-IFPTA+vaccine was accompanied with a significant reduction of plasma levels of total cholesterol (TC), LDL-C, and VLDL-C. Interestingly, L-IFPTA+vaccine could considerably reduce atherosclerotic lesion size and intima to media thicknessin hypercholesterolemic mice. Long-term evaluation of hypercholesterolemic vaccinated mice showed that L-IFPTA+vaccine was able to promote a long-lasting anti-PCSK9 antibody titration, which was paralleled by a significant reduction of LDL-C over 16 weeks post prime immunization (Figure). Splenocytes isolated from vaccinated mice indicated the reduced IFN-γ producing cells and the elevated IL-10 producing cells, suggesting immune safety of liposomal anti-PCSK9 vaccine.
Figure 1

Conclusions
L-IFPTA+vaccine induced efficient anti-PCSK9 antibodies which could exert long-term therapeutic effect on hypercholesterolemia and atherosclerosis in mice, revealing a feasible vaccine-based approach for managing hypercholesterolemia and cardiovascular disease.
P6195Nanoliposomal anti-PCSK9 vaccine induces long-term and safe protection against atherosclerosis in C57BL/6 mouse
Authors: Momtazi-Borojeni A A , Jaafari M R , Badiee A A , Banach M , Sahebkar A A 
Published: October 2019

Abstract

Background
Proprotein convertase subtilisin/kexin 9 (PCSK9) can increase plasma levels of low-density lipoprotein (LDL) cholesterol (LDL-C) through reducing protein levels of liver LDL receptor (LDLR). PCSK9 inhibition has been found to efficiently alleviate hypercholesterolemia.

Purpose
In the present study, we prepared nanoliposomal anti-PCSK9 vaccine and evaluated its protective effects against hypercholesterolemia and atherosclerotic plaque formation in C57BL/6 mice fed on atherogenic diet.

Methods
Nanoliposome formulation containing 1,2-Dimyristoyl-sn-glycero-3-phosphorylcholine (DMPC), 1,2-Dimyristoyl-sn-glycero-3-phosphorylglycerol (DMPG) and cholesterol (Chol) were prepared using the lipid-film hydration method, and used as the vaccine delivery system. Immunogenic peptide called Immunogenic Fused PCSK9-Tetanus (IFPT) was exhibited on the surface of nanoliposome carriers by using DSPE-PEG-Maleimide lipid (L-IFPT) and adsorbed to Alum adjuvant (L-IFPTA+). The prepared vaccine formulations IFPT, L-IFPTA+, IFPTA+, IFPT, and empty liposome as the negative control were subcutaneously administrated four times with a bi-weekly interval in C57BL/6 mice fed on atherogenic diet. Protein levels of liver LDLR, lipid profile, plasma levels of anti-PCSK9 antibody, plasma concentration of PCSK9 protein, and effect of anti-PCSK9 antibody on PCSK9-LDLR interaction were measured in the vaccinated mice. Aortic arch atherosclerotic lesions were studied using hematoxylin and eosin staining. To determine inflammatory response, splenic CD4+producing IL-4 and IFN-γ were evaluated using flow cytometry analysis.

Results
Among formulated vaccines, the L-IFPTA+vaccine could generate the highest IgG anti-PCSK9 antibody in the vaccinated hypercholesterolemic mice. The generated anti-PCSK9 antibodies inhibited interaction of PCSK9 with LDLR through targeting plasma PCSK9, whereby protein levels of liver LDLR was elevated in the vaccinated mice. As reveled by lipid profile analysis, liposomal vaccines, with more extent the L-IFPTA+vaccine, could significantly decrease plasma TC and LDL-C in hypercholesterolemic mice. Of note, L-IFPTA+ vaccine could reduce size and severity of atherosclerotic lesion in the aorta arch. Importantly, long-term (48 weeks) follow-up of hypercholesterolemic vaccinated mice revealed that L-IFPTA+vaccine could induce a long-lasting humoral immune response against plasma PCSK9, which was accompanied with a significant decrease of TC and LDL-C (Figure). Additionally, Anti-inflammatory Th2 cells and IL-4 cytokine were significantly elevated in splenic cells isolated from hypercholesterolemic vaccinated mice.
Figure 1

Conclusions
L-IFPTA+vaccine can promote long-lasting, functional and safe anti-PCSK9 antibodies in hypercholesterolemic C57BL/6 mice, revealing long-term protective effect against hypercholesterolemia and atherosclerosis.
P6204Oral vaccination of Lactococcus lactis expressing Ling Zhi 8 protein prevents nonalcoholic fatty liver and early atherogenesis in cholesterol-fed rabbits
Authors: Lin W W , Lee M F , Lin S J , Wu T J 
Published: October 2019

Abstract

Background
Atherosclerosis is an inflammatory disease characterized by lipid deposits in the subendothelial space leading to severe inflammation. Nonalcoholic fatty liver disease (NAFLD) shares several risk factors with atherosclerosis. Epidemiology studies have indicated that NAFLD may be an independent risk factor for atherosclerosis. Anti-inflammation therapy by inhibiting IL-1β led to a significantly lower cardiovascular event rate in recent clinical trial (CANTOS trial). Ling Zhi 8 (LZ8) is an immunomodulatory protein that possesses a broad range of pharmacological properties, including anti-inflammatory activities.

Methods and findings
In this study, we developed an oral vaccination of Lactococcus lactis expressing LZ8 protein in a nisin-controlled gene expression system and investigated its anti-inflammation properties. Experimental rabbits received commercial rabbit chow supplemented with 2% cholesterol for 5 weeks and recombinant LZ8 L. lactis vaccine once a day on weekdays. The expression of IL-1β in the aorta (Figure A) was significantly suppressed after LZ8 vaccination. Moreover, in hematoxylin and eosin staining of the aorta, the intima-medial thickness was decreased, and foam cells were significantly reduced in the sub-endothelial space (Figure C). LZ8 also inhibited the expression of IL-1β in the liver (Figure B), decreased fat droplet deposits and infiltration of inflammatory cells (Figure D), and improved liver function by decreasing liver enzymes.
Figure 1

Conclusions
Our results suggest that LZ8 could be used as a therapeutic tool to improve both atherosclerosis and NAFLD due to its anti-inflammatory effect.

Acknowledgement/Funding
TCVGH-1067317C, TCVGH-1063108C
P6206Death, debility, and destitution following recurrent myocardial infarction in older adults
Authors: Levitan E , Poudel B , Zhao H , Bittner V , Safford M M , Jackson E , Monda K L , Muntner P 
Published: October 2019

Abstract

Background
Most prior research on outcomes among older adults with established cardiovascular diseases focuses on recurrent events and hospitalizations. However, older adults value financial security and functional independence in addition to these disease-focused metrics. Recurrent cardiovascular events may increase risk of long-term nursing home residence and financial strain.

Purpose
To compare the risk for death, debility (long-term residence in a nursing home), and destitution (eligibility for health insurance programs for impoverished individuals) among older adults with recurrent myocardial infarction (MI) and controls.

Methods
We conducted a retrospective cohort study using administrative data from the United States Medicare program, a health insurance program for older adults. Among all patients who experienced a first overnight hospitalization with a discharge diagnosis of MI between 1 January 2007 and 30 June 2016, we identified patients with a recurrent MI hospitalization. Additionally, we selected controls from the same population of patients with MI, matched on calendar year of the initial MI and days since the initial MI. We included 194,481 patients aged 66 years and older with recurrent MI hospitalizations and 777,924 controls. Patients were followed for death, debility, and destitution until 31 December 2016. We used Kaplan-Meier curves and Cox proportional hazards models adjusted for sociodemographic factors, comorbidities, and healthcare utilization to compare patients with recurrent MI and matched controls.

Results
The average age of the population was 80.0 (standard deviation 8.3) years and 56.7% were women. Patients with recurrent MI were more likely to have a history of diabetes, chronic kidney disease, heart failure and peripheral artery disease than controls. The cumulative incidence of death, debility, and destitution were all higher among patients with recurrent MI than their matched controls (Figure). Comparing patients with recurrent MI to controls, the hazard ratios (95% confidence intervals) were 2.11 (2.09–2.13) for death, 0.92 (0.89–0.94) for debility, and 1.34 (1.29–1.39) for destitution after multivariable adjustment.
Death, debility, and destitution

Conclusion
Preventing recurrent MIs has the potential to reduce not only mortality but also destitution.

Acknowledgement/Funding
Amgen, Inc
P6208VEgetaRian Diet in patients with Ischemic heart disease (VERDI): an open-label, randomized, prospective, cross-over study
Authors: Djekic D , Carlsson F , Landberg R , Sarnqvist C , Cao Y , Tremaroli V , Backhed F , Frobert O 
Published: October 2019

Abstract

Background
A vegetarian diet (VD) in patients diagnosed with ischemic heart disease (IHD) may reduce future cardiovascular risk.

Purpose
The study hypothesis was that patients diagnosed with IHD can benefit from a VD assessed by multiple risk markers for this type of disease.

Methods
In a crossover study patients diagnosed with IHD, treated by percutaneous coronary intervention and on optimal medical therapy were randomly allocated to a 4-week intervention with ready-made (lunch and dinner) isocaloric VD or meat diet (MD). The primary outcome was change in oxidized low-density lipoprotein cholesterol (LDL-C) levels. Secondary outcomes were difference in changes of blood lipids, weight, body mass index (BMI), blood pressure, heart rate, glycated haemoglobin (HbA1c), number of participants reaching guideline target values, quality of life, gut microbiota, and trimethylamine N-oxide between the two interventions.

Results
31 participants were recruited (median age: 67 years, male sex: 93.5%). Significant between-intervention differences (VD vs MD) were found in oxidized LDL-C (−2.73 U/L; p=0.015), total cholesterol (TC) (−0.13 mmol/L, p=0.01), LDL-C (−0.10 mmol/L; p=0.02), weight (−0.67 kg, p=0.008) and BMI (−0.21 kg/m2, p=0.009). After VD, numerically more subjects reached guideline LDL-C target values (87% vs 77%) but this did not reach statistical significance (p=0.07). During VD intervention the diet led to a significant reduction in oxidized LDL-C, TC, LDL-C, HDL-C, ApoB, and ApoB/ApoA1 ratio.

Conclusions
Our results suggest that in patients with IHD a VD compared to a MD, lowers oxidative stress, improves lipid profile and lowers BMI.

Acknowledgement/Funding
This study is partially funded by ALF and the Swedish Heart and Lung Foundation.
P6210Pathway of care and life course of patients with recurrent ST-elevation myocardial infarction
Authors: Fraticelli L , Kleitz O , Claustre C , Eydoux N , Peiretti A , Bonnefoy-Cudraz E , El Khoury C 
Published: October 2019

Abstract

Background
We hypothesized that patients having experienced one coronary event in their life must present differences in their pathway of care in the acute phase and within 12-month life course.

Purpose
This study aimed to compare pathways between current and recurrent Myocardial Infarction.

Methods
All patients from the OSCAR registry with ST Elevation Myocardial Infarction (STEMI) as final diagnosis from 2013 to 2016 were included. We defined recurrent STEMI as a reinfarction occurring within 12-month post-current-STEMI and STEMI with prior MI occurred before the inclusion date.

Results
Recurrent STEMI called more often the medical dispatch center (71.32% vs 62.36%, p<0.0001) and benefited from out-of-hospital medical care by Emergency Mobile Services (67.07% vs 59.70%, p=0.0007). The hospital management delays did not differ but the delay symptom-ECG tended to be 26 minutes longer for recurrent STEMI admitted directly to the emergency department (182 [109; 314] vs 156 [89; 291], p=0.0510). They also underwent less percutaneous coronary interventions (PCI) (90,24% vs 95,07%, p<0.0001). At 12 months post-discharge, we observed a better adherence to BASIC-treatment (Beta-blockers, Anti-platelet medications [aspirin, clopidogrel, prasugrel], Statins and Converting Enzyme Inhibitor Combination-treatment) for recurrent STEMI (64,06% vs 52,98%, p=0.0062) but the key lifestyle interventions were less applied.

Conclusion
Comparison of care and life course of current and recurrent STEMI highlighted a different use of pre-hospital care and hospital resources. They also showed better adherence to BASIC-treatment during recurrent events compared to current STEMI.

Acknowledgement/Funding
The RESCUe Network is funded by the Regional Agency for Health from Auvergne-Rhône-Alpes region (Agence Régionale de Santé Auvergne-Rhône-Alpes).
P6221Salt consumption as a predictor of cardiovascular events among hypertensive patients: a 5-year follow-up study
Authors: Kasiakogias A , Tsioufis C , Konstantinidis D , Leontsinis I , Iliakis P , Koumelli A , Konstantinou K , Liatakis I , Siafi E , Tousoulis D 
Published: October 2019

Abstract

Background/Introduction
Salt intake is linked to hypertension but data on its association with incident cardiovascular events, especially among hypertensives, is limited.

Purpose
To examine the prospective association of different salt consumption levels with cardiovascular morbidity in a hypertensive population.

Methods
We followed 2130 hypertensive patients (age 57±12 years, 11.2% untreated) without a history of cardiovascular disease for a mean period of 5.3±3.3 years. At the baseline examination, salt intake was evaluated by a structured validated questionnaire. Accordingly, the study population was divided into three groups: hypertensives with a low (1079 patients, 51% of the population), a moderate (895 patients, 42%) and a high salt consumption (146 patients, 7%). During follow-up, patients underwent clinic visits at least yearly for management of hypertension and risk factors. The outcome studied was the composite of non-fatal cardiovascular events.

Results
The composite endpoint (19 strokes and 65 cases of coronary artery disease) occurred in 84 patients (3.9%). At baseline, increasing salt consumption was significantly associated with age, body mass index, office blood pressure and renal function. Unadjusted Cox regression analysis showed that, compared to the reference group, the risk for cardiovascular morbidity was similar in patients with moderate salt consumption (HR: 1.1, 95% CI: 0.71–1.77) but significantly higher in patients with high salt consumption (HR: 2.12, 95% CI: 1.09–4.38). This pattern was clearly sustained after adjusting for multiple risk factors including baseline blood pressure levels.

Conclusions
Among hypertensive patients, heavy salt consumption is associated with an increased cardiovascular risk, while moderate consumption does not affect patient outcome.
P6224The combined influence of waist and hip circumference on mortality risk in a large cohort of European and Australian adults: moving beyond BMI, Waist and WHR as measures of obesity
Authors: Soderberg S 
Published: October 2019

Abstract

Background
Previous research has demonstrated that waist circumference (WC) and hip circumference (HC) are both important predictors of mortality, independent of established risk factors. Their combined influence on risk, and whether they are superior to established obesity measures, has not been thoroughly examined in large cohorts.

Purpose
We investigated whether WC and HC are better joint predictors of all-cause and cardiovascular disease (CVD) mortality than individual measures of obesity: WC, HC, waist hip ratio (WHR), waist-to-height ratio (WHtR), a body shape index (ABSI), and body mass index (BMI).

Methods
We used data from 90,487 males and females, 25–74 years of age with no prior history of CVD, from the MOnica Risk, Genetics, Archiving and Monogram (MORGAM) project. Hazard mortality ratios (HR) were estimated using sex-specific Cox models stratified by cohort/country, with age as the time scale. Obesity measures were categorized based on sex specific sample means and standard deviations (SD). All final fully adjusted models included baseline age, total and HDL cholesterol, systolic blood pressure,antihypertensive drugs, current smoker and diabetes.

Results
During a mean follow-up of 11 years, 9105 all-cause and 2577 CVD deaths were recorded. All obesity measures were found to be associated with all-cause and CVD death after taking account of known CVD risk factors, with the strongest statistical evidence of associations seen for WC and HC combined and ABSI. J- or U-shaped associations with mortality were observed for BMI, WC, HC and WHtR for both males and females, and WHR and ABSI for males. Monotonic associations with mortality were observed for WHR and ABSI for females. For WC and HC combined, HC was an important predictor of death among those with smaller WC (≤1 SD above the mean: below 99cm in women and 106cm in men), with larger HCs associated with reduced risk. No additional increase in mortality risk was found to be associated with HC for those with a WC >1SD above the mean. Of those who would not have been identified as being at higher risk based on their WC alone, 55.7% (n=8350) of females and 30.6% (n=4510) of males are identified as being at higher risk when their smaller HC is taken into consideration.

Conclusion
The use of single measurements of obesity such as BMI, WC or WHR does not capture the complex relationship between body shape and risk of premature death. Both WC and HC, but not as a ratio, should be used by clinicians to help identify those at increased risk of premature death.

Acknowledgement/Funding
Individual grants to included cohorts