bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cholesterol remnants distribution in patients admitted for acute coronary syndrome
Authors: Cordero A , Escribano D , Alvarez-Alvarez B , Martinon J , Garcia-Rondeja F , Rodriguez-Manero M , Bertomeu-Gonzalez V , Cazorla D , Moreno-Arribas J , Quintanilla M A , Lopez Ayala J M , Zuazola P , Gonzalez-Juanatey J R 
Published: October 2022

Abstract

Background
Cholesterol remnants have been identified as one of leading lipid measurements associated with the incidence of coronary heart diseases. Nonetheless, there is scarce evidence on cholesterol remnants distribution in patients with acute coronary syndrome (ACS).

Methods
We included all consecutive patients admitted for ACS in two different centers. Cholesterol remnants were calculated by the equation: total cholesterol minus low-density lipoprotein cholesterol (LDLc) minus high-density lipoprotein cholesterol (HDLc) and values ≥30 were considered high. Premature ACS was defined in patients presenting with age &lt;55 for men or &lt;65 for women. Correlation weres assessed by linear regression and predictive models were obtained after logistic binary regression.

Results
We included 7,479 patients, mean age 66.68 (13.02), 2,062 (27.57%) women, mean body mass index (BMI) 28.60 (4.64) kg/m2, 2088 (27,92%) with diabetes and 2,726 (36.45%) admitted for ST-elevation ACS. Median (interquartile range) remnants level was 28 mg/dl (21–39) and 3,429 (45.85%) patients had levels ≥30 mg/dl. Significantly higher levels of remnants were observed in patients with diabetes, current smokers, BMI &gt;30 kg/m2, absence of previous cardiovascular disease or premature ACS. No gender differences were observed in remnants level. Age (r: −0.29) and BMI (r: 0.44) were the variables more strongly correlated. As shown in the figures, at any given age, the risk of having cholesterol remnants ≥30 increased with higher BMI.
In-hospital mortality was 3.75% (280 patients). After adjustment by age, gender, previous cardiovascular disease and GRACE score, cholesterol remnants were not associated to higher mortality risk (OR: 0.89 95% CI 0.64–1.10; p=0.21)

Conclusions
Elevated cholesterol remnants is highly prevalent in patients admitted for ACS and their levels inversely correlate with age and positively with body mass index. We propose a risk matrix for estimating the probability of having cholesterol remnants ≥30. Elevated cholesterol remnants were not associated to higher in-hospital mortality risk.

Funding Acknowledgement
Type of funding sources: None.
Lipoprotein(a) testing in clinical practice: real-life data from a large health-care provider
Authors: Zafrir B , Aker A , Saliba W 
Published: October 2022

Abstract

Background
Evidence support a causal role of lipoprotein(a) [Lp(a)] in the development of atherosclerotic cardiovascular disease (ASCVD). Novel treatment options are emerging and recent guidelines recommend screening Lp(a) levels at least once during lifetime. However, significant variance exists regarding the incorporation of Lp(a) into patient care.

Purpose
To investigate patterns of Lp(a) measurement in a large health maintenance organization (HMO) and describe clinical characteristics associated with elevated Lp(a) levels.

Methods
Retrospective analysis of all Lp(a) laboratory tests performed between January 2015 and December 2021 in a single HMO providing health care for approximately 4.6 million insured members.

Results
Overall, 4,539 individuals were tested for Lp(a). Analysis was limited to the adult population (n=3900). Number of persons tested yearly increased progressively from 89 in the year 2015 to 1523 in 2021. Mean age was 55±15 years (39% females), 15% had family history of coronary disease, 40% ischemic heart disease, 7% prior stroke and 9% peripheral artery disease (PAD). Baseline low-density lipoprotein cholesterol (LDL-C) &gt;190 mg/dl was evident in 21% of patients. Lp(a) level &gt;125 nmol/l (∼50 mg/dl) was noted in 21.5%. In a multivariable logistic regression model, prior myocardial infarction (odds ratio 1.38, 95% confidence interval 1.16–1.64), PAD (1.29, 1–1.68), peak LDL-C&gt;190 mg/dl (1.35, 1.12–1.62) and use of statins (1.54, 1.28–1.85), were independently associated with elevated Lp(a) levels &gt;125 nmol/l, whereas an inverse association was seen with obesity (0.74, 0.62–0.88). Of the patients with elevated Lp(a), 72.4% were treated with statin and/or ezetimibe and 1.9% with PCSK9 inhibitors.

Conclusions
The reporting of Lp(a) levels is increasing, though it is still measured in a small portion of the population. Presence of ASCVD and severe hyperlipidemia may identify patients that should be considered for screening for increased Lp(a) levels. The use of PCSK9 inhibitors in those with elevated Lp(a) is yet considerably low.

Funding Acknowledgement
Type of funding sources: None.
Risk stratification and lipid evaluation in Mexican patients, evidence of lipid and cardiovascular analysis of a real world data registry (REMECAR)
Authors: De Los Rios Ibarra M O , Leiva-Pons J L , Rodriguez-Reyes H , Alcocer-Gamba M A , Cortes-Lawrenz J , Vizcaino-Rios F M , Barragan-Luna J , Farjat-Ruiz J I , Virgen-Carrillo L R , Lugo-Gavidia L M 
Published: October 2022

Abstract

Background and purpose
Dyslipidaemia is a significant risk factor for cardiovascular disease in the Mexican population. This analysis aims to describe the baseline LDL-c levels of patients at cardiovascular clinics and evaluate the proportion of them who achieved their risk-based LDL-c goals as recommended by 2021 ESC prevention guidelines.

Methods
The REMECAR registry is an observational study of patients attending a specialized cardiovascular clinic for their first visit. The cardiovascular risk was retrospectively determined using the 2021 ESC guideline stratification and the SCORE2 and SCORE-OP.

Results
A total of 5,443 patients were included in the analysis. Within this population, 55.96% presented as very high, 39.98% as high and 4.06% as moderate to low risk. 63% of the participants were not on any lipid lowering treatment at entry, while 12.4% were receiving high intensity statin therapy. Patients presenting with established atherosclerotic cardiovascular disease had a mean LDL-c of 90.9±40.7 mg/dL. Of these, 14.1% were achieving LDL-c levels of 70–50 mg/dL and 19.3% were achieving LDL-c levels &lt;55mg/dL (Figure 1B) In diabetic patients at very high risk, only 25.7% reached their LDL-c goal. Finally, in patients without another risk factor and very high-risk evaluated by SCORE2 & SCORE-OP, only 14% of patients achieved their LDL-c goals.

Conclusions
A significant number of patients were not receiving lipid lowering therapy. Furthermore, in those who were, a significant portion did not achieve LDL-c recommended thresholds. Our results underline the urgent need to improve the prescription and optimisation of lipid lowering therapy as the current management appears to be insufficient for achieving optimal recommended goals. Identifying key barriers in lipid management is fundamental to establishing better strategies and health system policies to reduce cardiovascular risk.

Funding Acknowledgement
Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): AMGEN
Quantification of left ventricular fibrosis in arrhythmic mitral valve prolapse patients: comparison of different semi-automated techniques assessed by cardiac magnetic resonance
Authors: Cecere A , Cipriani A , Ravagnin A , Graziano F , Brunetti G , De Conti G , Motta R , De Lazzari M , Iliceto S , Perazzolo Marra M 
Published: October 2022

Abstract

Background
Left ventricular (LV) fibrosis has a key role in arrhythmogenesis in mitral valve prolapse (MVP) patients. Cardiac magnetic resonance (CMR) demonstrated able to clearly identify LV fibrosis with the post-contrast late gadolinium enhancement (LGE) images. Despite the pivotal role of LV fibrosis in the arrhythmogenesis, a quantification and identification of reproducible method able to accurately measure LGE in arrhythmic MVP patients has not been recognized.

Purpose
We aimed to measure and compare different semi-quantitative methods for LGE quantification assessed by CMR, in order to identify the most reproducible one, in arrhythmic MVP patients.

Methods
66 arrhythmic MVP patients with normal systolic function and without significant regurgitation were enrolled. Semi-automated gray-scale thresholding technique using full with at half maximum (FWHM) and 2, 3 and 5 standard deviation (SD) above the remote myocardium were used and compared with visual assessment (Fig. 1).

Results
LGE was identified in 41 arrhythmic MVP patients (62%) and quantified (Fig. 2). The mean quantity of LGE visually assessed was 2.40±1.07% or 1.40±0.82 g. With FWHM, LGE resulted 3.56±1.23% or 1.99±1.13 g. Using thresholding, the mean LGE quantity was 9.2±3.1% or 4.82±2.28 g for 2-SD, 5.72±1.75% or 3.06±1.47 g for 3-SD and 2.36±0.99% or 1.29±0.79 g for 5-SD. The 5-SD measurement in percentage demonstrated a good correlation with LGE quantification visually assessed (2.402±1.075 vs 2.363±0.9909, p: 0.543). Despite all semi-quantitative methods for LGE quantification demonstrated a good intra and inter-observer agreement, the 5-SD threshold quantification, both in percentage and in grams, revealed the less intra-observer (respectively, ICC: 0.976 and 0.966) and inter-observer variability (respectively ICC: 0.948 and 0.935) when compared with visual assessment.

Conclusion
This is the first study that quantified and compared different CMR semi-automated methods for LGE assessment in a population of arrhythmic MVP patients. The 5-SD gray-scale threshold technique in percentage revealed the best correlation with the visual assessment and an optimal reproducibility.

Funding Acknowledgement
Type of funding sources: None.
The immunogenic potential of PCSK9 peptide vaccine in mice
Authors: Ataei S , Momtazi-Borojeni A A , Jaafari M R , Banach M , Sahebkar A A 
Published: October 2022

Abstract

Background
Proprotein convertase subtilisin/Kexin 9 (PCSK9) is a serum protein expressed by liver cells that regulates plasma low-density lipoprotein cholesterol (LDL-C) levels by modulating LDL receptors (LDLR). Recent studies of our group indicated the efficient immunogenicity of the nanoliposomal PCSK9 peptide vaccine in different animal models.

Purpose
Herein, we sought to evaluate the immunogenic potential of the non-liposomal form of the vaccine due to its simplicity of processing and lower production cost.

Methods
PCSK9 immunogenic peptide was prepared by linking a short PCSK9 peptide to a tetanus peptide as B and T cell epitopes, respectively. The immunogenic peptide and 0.4% alum adjuvant, in a 1:1 ratio, were mixed thoroughly and homogeneously prior to administration as vaccine formulation. In order to assess the humoral immune response, mice were inoculated subcutaneously four times at bi-week intervals. Immunized animals' blood was sampled two weeks after the last injection. The titers of the anti-PCSK9 antibodies in the serum of vaccinated mice were evaluated using the ELISA method. ELISA was also used to investigate the effects of anti-PCSK9 vaccination on PCSK9 serum concentrations and its interaction with LDL receptor (LDLR).

Results
ELISA analysis showed significant induction of IgG antibody titers by PCSK9 peptide vaccine in vaccinated mice compared to the control group (586±12000 and 642±11566 in male and female vaccinated mice, respectively, p&lt;0.001). No significant difference was found between the male and female vaccine groups (p&gt;0.05). Mechanistic analyses showed that vaccine-induced antibodies decreased serum PCSK9 concentration in vaccine groups compared to the control group (in male mice by 26±5 ng/mL, p&lt;0.01 and female mice by 29±5 ng/mL, p&lt;0.01). Serum concentrations of PCSK9 in control and vaccine groups were found to be 131±8.6 ng/mL and 102±8.1 ng/ml in male mice, and 124±6 ng/ml and 98±10 ng/ml in female mice, respectively. Moreover, vaccine-induced antibodies inhibited the PCSK9/LDLR interaction in the presence of serum from vaccinated mice compared to control mice serum (in male and female groups by 34% and 26%, respectively). The PCSK9 peptide vaccine significantly reduced LDL-C in immunized mice in both male (16.93±2.5 mg/dL, p=0.001) and female groups (22±2.7 mg/dL, p=0.001) compared with the control group.

Conclusions
According to our results, the PCSK9 peptide vaccine stimulates the humoral immune response in albino mice to produce active antibodies that inhibit plasma PCSK9 resulting in plasma LDL-C reduction.

Funding Acknowledgement
Type of funding sources: None.
Machine learning can accurately detect abnormal aortic valves in CMR
Authors: Vimalesvaran K , Uslu F , Zaman S , Howard J , Bharath A , Cole G 
Published: October 2022

Abstract

Background
Improving the efficiency of CMR by acquiring fewer, and more targeted sequences, would improve the diagnostic yield and reduce patient recalls. An AI-assisted clinical decision support system (CDSS) could deliver this efficiency using adaptive scanning protocols which replicate the expertise of highly trained clinicians. Normal aortic valve anatomy on the three-chamber (3CH) cine CMR is a guide to rationalising subsequent sequences, and therefore is a suitable base case for developing an AI-CDSS for CMR.

Purpose
We propose a machine learning approach to differentiate between normal and abnormal aortic valves from the 3CH cine.

Methods
We curated a unique expert-annotated dataset of 1221 frames from eighty CMR studies. For each frame, AV landmarks (two hinge points and two leaflets), and stenotic and regurgitant jets were labelled by three cardiologists.
We then tested two AI models (Figure 1) to detect these AV abnormalities: A) a convolutional neural network (CNN), and B) a random forest approach.
A) Using heat map regression, the AV was localised, and the jets (if present) were identified as pathological curves. We then tracked and quantified the curves in the estimated heatmaps based on their proximity, the length, orientation and angle with respect to the hinge points.
B) We used a random forest approach to classify cases as normal or abnormal by using the characteristics of estimated pathological curves obtained from the heat map regression output.
We trained and evaluated our models on an unseen dataset of 1017 CMR studies obtained from different scanner types across three NHS hospitals. Each CMR study report was manually assigned a binary ground truth label for a normal or abnormal AV. In total 496/1017 patients had an abnormal AV. Of those abnormal cases, 184 patients had aortic stenosis, 222 aortic regurgitation and 90 cases had mixed valve disease.
We assessed the classification performance of our method with accuracy and an F1 score – a composite of precision and recall, where 1 is perfect; and heatmap regression performance for curves with mean absolute error.

Results
This machine learning approach classified abnormal aortic valves with good agreement to the ground truth labels with mean accuracy of 0.93 (representing approximately 451/496 patients) and mean F1 score of 0.91. The AV hinge points were localised with a mean distance error of 3.5 pixels. This was despite the small size of expert labelled data.

Conclusion
This machine learning solution successfully differentiated between normal and abnormal aortic valves from routine 3CH cine CMR views. More labelled datasets will enable further classification of pathology and severity, and greater accuracy. Our results represent an important stepping stone towards an AI-assisted CDSS for CMR.

Funding Acknowledgement
Type of funding sources: Other. Main funding source(s): This work was supported by the UKRI CDT in AI for Healthcare http://ai4health.io
Patients with pseudoxanthoma elasticum (PXE) do not have dyslipidemia
Authors: Harmsen I M , Visseren F L J , Kok M , De Jong P A , Spiering W 
Published: October 2022

Abstract

Background
Pseudoxanthoma elasticum (PXE) is a rare genetic disease caused by low inorganic pyrophosphate and is characterized by medial arterial calcification, leading to peripheral arterial disease and ischemic cerebral disease. Animal studies and small human studies have reported an association between PXE and dyslipidemia and therefore suggest that atherosclerosis is a second pathway contributing to cardiovascular disease in PXE patients. The association between PXE and dyslipidemia was however not consistent across these studies and there are several biological hypotheses proposed where the affected gene in PXE (ABCC6) could affect the cholesterol pathway: ABCC might influence HMA-CoA reductase – and increase total cholesterol and LDL-c – on one hand, but there is also evidence that points toward influence of ABCC6 on the reversed cholesterol pathway, influencing HDL-c. This study is important to analyze if PXE subjects, from the larges PXE cohort in the world, indeed do have a different a different lipid profile compared to well matched controls.

Purpose
To evaluate whether PXE patients have a different lipid profile compared to non-PXE patients.

Methods
A cross-sectional patient-control study was done at the Dutch Expertise Center for PXE in the University Medical Center Utrecht. Patients were all diagnosed conform the Plomp cirteria. The control population consisted of acquaintances of PXE patients, excluding first and second-degree relatives. Total cholesterol, LDL-c, HDL-c and triglycerides were assessed in both patients and controls and if lipid-lowering treatment (LLT) was used pre-treatment levels were calculated using known effects of LLT on lipids.
To eliminate the imbalances between patients and controls, we used Coursened Exact Matching (CEM), to investigate the effect of PXE on lipids.

Results
The study population included 323 PXE patients and 57 controls. Their characteristics are displayed in Figure 1.
After CEM 186 patients (weighted means: age 57.8±9.9 years, 58% females, BMI 25.5±2.9 kg/m2) and 52 controls (age 57.3±43.1 years, 58% females, BMI 25.5±17 kg/m2) were left for analyses. The univariate, weighted regression analysis of the effect of having PXE on lipid profile shows that the differences in lipids between patients and controls were 0.22 mmol/L for total cholesterol (p=0.299), 0.15 mmol/L for LDL-c (p=0.524), 0.07 mmol/L for HDL-c (p=0.314) and 0.10 mmol/L for triglycerides (p=0.433).
A sensitivity analysis where only the crude values of untreated subjects were included in the analysis showed that LDL-c was sginficantly lower in PXE-patients. Probably due to the fact that only the very healthy PXE patients were included.

Conclusion
There are no differences in levels of total cholesterol, LDL-c, HDL-c, and triglycerides between PXE patients and matched controls.

Funding Acknowledgement
Type of funding sources: None.
Cost-effectiveness of cholesterol-lowering drugs for secondary cardiovascular prevention in the UK: ezetimibe, evolocumab, and alirocumab
Authors: Michaeli D T , Michaeli J C , Boch T , Michaeli T 
Published: October 2022

Abstract

Background
Despite statin treatment, patients with elevated low-density lipoprotein cholesterol (LDL-C) levels remain at high risk for acute cardiovascular events. Ezetimibe, evolocumab, and alirocumab were consequently developed to reduce the risk of recurrent ischemic events in patients with established cardiovascular diseases by 6%, 15%, and 15%, respectively. However, these novel treatments must demonstrate both clinical efficacy and cost-effectiveness to promote long-term adoption by patients, physicians, and insurers.

Objective
To assess the cost-effectiveness of statins in combination with ezetimibe, evolocumab, and alirocumab for secondary cardiovascular prevention from the perspective of England's National Health Service (NHS).

Methods
The incidence of major adverse cardiovascular events, including, myocardial infarction, stroke, angina, and coronary revascularization, was simulated with a Markov cohort model. The model was populated with transition probabilities and hazard ratios derived from cardiovascular outcome trials for statin combinations with ezetimibe (IMPROVE-IT), evolocumab (FOURIER), and alirocumab (ODYSSEY). Costs and utilities were retrieved from previous literature. Principle outcomes of interest were the incremental cost-effectiveness ratios (ICER) per quality-adjusted life year (QALY) gained in 2021 Great Britain Pounds (£). Univariate, scenario, willingness-to-pay, and probabilistic sensitivity analyses were conducted to assess the robustness of results.

Results
For secondary cardiovascular prevention, ezetimibe in combination with statins increased QALYs gained by 0.60 at cost reductions of −£2,529 (ICER: −4,231 £/QALY) per patients compared to statin monotherapy. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors provided incremental QALYs of 0.53 and 0.86 at costs of £45,279 and £46,375 for evolocumab (ICER: 75,283 £/QALY) and alirocumab (ICER: 40,708 £/QALY), respectively. At the NHS' willingness-to-pay threshold of 30,000 £/QALY, there is 100% probability for ezetimibe and 0% probability for PCSK9 inhibitors to be cost-effective in secondary prevention. Results remained robust under univariate, scenario, and probabilistic sensitivity analyses.

Conclusions
Ezetimibe is cost-effective for secondary cardiovascular prevention at an annual price of £346 in the UK. For PCSK9 inhibitors, discounts of −37% to −53% on alirocumab's (£4,412) and evolocumab's (£4,467) prices are necessary to achieve cost-effectiveness.

Funding Acknowledgement
Type of funding sources: None.