bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect on cholesterol remnants and residual lipid risk with PCSK9 inhibitors: the LIPID-REAL Registry
Authors: Fernandez Del Olmo R , Cordero A , Cortez Quiroga G , Romero-Menor C , Facila L , Rondan J , Bello Mora M C , Sandin M , Valle A , Freixa R , Blanch P , Baneras J , Rodriguez-Manero M , Gonzalez-Juanatey J R 
Published: October 2022

Abstract

Background
Monoclonal antibodies that inhibit the proprotein convertase subtilisin/kexin type 9 (PCSK9) reduce low-density lipoprotein cholesterol (LDLc) by 55%, regardless of baseline treatments. Nonetheless, the effect of other lipid parameters, as cholesterol remnants or, the so-called residual lipid risk, are unknown.

Methods
Multicenter and retrospective registry of patients treated with PCSK9 inhibitors from 14 different hospitals from Spain. Before and on-treatment lipid parameters were recorded. Cholesterol remnants were calculated by the equation: total cholesterol minus LDLc minus HDLc and values ≥30 were considered high. Residual lipid risk was estimated by 1) the estimation of LDL particle size, by the triglycerides/HDLc ratio (TG/HDL) and values &lt;2 were assumed as low and dense LDL particles; 2) total cholesterol/HDLc (TC/HDL) and values &gt;3 were considered high; and; 3) the triglycerides-to-glucose (TG/Gluc) index, obtained as the natural logarithm of (triglycerides * glucose/2)

Results
A total of 652 patients were analyzed, mean age 60.0 (10.5) years and 161 (24.69%) women. Baseline LDLc was 149.2 (49.9) mg/dl, cholesterol remnants 29.9 (20.3) mg/dl, TG/HDL 3.9 (4.1), TC/HDL 4.9 (1.9) and TG/Gluc index 8.9 (0.7). Most patients (92.3%) were on statins; 54.8% with ezetimibe, 8.5% with fibrates.
Evolocumab was initiated in 318 (56.6%) patients; 229 (40.7%) alirocumab 75 mg and 15 (2.7%) alirocumab 150 mg. Median time to second blood determination were 187.5 (IQR 101–242) days. Mean on-treatment LDLc was 67.46 (45.78) mg/dl what represented a 55% reduction. As shown in the figure, significant reduction in cholesterol remnants (p=0.017), TG/HDL ratio (p=0.020), TC/HDL ratio (p&lt;0.001) and TG/Gluc index (p&lt;0.001). The percentage of patients with remnants &gt;30 mg/dl decreased: 34.62% to 30.07 (p&lt;0.01). Significant reductions were also observed in the percentage of patients with TG/HDL &gt;2 (71.25% to 61.98%; p&lt;0.01) or TC/HDL &gt;3 (94.28% to 38.97%; p&lt;0.01)

Conclusions
This multicenter and retrospective registry of real-world patients treated with PCSK9 inhibitors demonstrates a positive effect on cholesterol remnants and lipid-residual risk beyond LDLc reductions.

Funding Acknowledgement
Type of funding sources: None.
Left ventricular remodeling in aortic stenosis patients referred for surgical aortic valve replacement
Authors: R Santos R , Abecasis J , Maltes S , Mendes G S , Oliveira L , Horta E , Guerreiro S , Freitas P , Ferreira A , Ribeiras R , Andrade M J , Cardim N , Gil V , Mendes M , Neves J P 
Published: October 2022

Abstract

Background
Left ventricular (LV) hypertrophy is a common expected finding in aortic stenosis (AS) patients. Cardiac magnetic resonance (CMR) plays an important role as a non-invasive method for determining LV mass and volume, and to characterize the LV remodeling response in AS.

Aim
To assess the prevalence, to describe the patterns and evolution of LV remodeling (by CMR) in AS patients referred for surgical aortic valve replacement (AVR).

Methods
Single-center prospective cohort of 132 consecutive patients (73 years [68–77 years], 49% men] with severe AS: mean transaortic pressure gradient (AVmean): 61±1.5 mmHg; aortic valve area (AVA): 0.7±0.1 cm2, referred for surgical AVR, with no previous history of ischemic cardiomyopathy. Before surgery, all patients underwent electrocardiogram, complete transthoracic echocardiogram (TTE) and CMR for LV assessment and tissue characterization (mean LV indexed mass [LVMi]: 80.3±26.5 g/m2; mean end-diastolic LV indexed volume [LVEDVi]: 84.4±24.5 mL/m2 and median geometric remodeling ratio [M/V]: 0.95 g/mL [IQR 0. 81–1.08 g/mL]). Patterns of LV remodeling were investigated before and after AVR by CMR measurements of LVMi, LVEDVi and M/V. Besides normal LV ventricular structure, four other patterns were considered: concentric remodeling, concentric hypertrophy, eccentric hypertrophy, and adverse remodeling (Figure 1).

Results
Overall, 43% (n=58) of the patients had concentric hypertrophy, 30% (n=40) concentric remodeling, 22% (n=29) normal ventricular geometry, 4% (n=5) eccentric hypertrophy and in two patients we observed an adverse remodeling pattern. AVR was performed in 80 patients. At the 3rd to 6th month post-AVR assessment, LV remodeling changed to: normal ventricular geometry in 46%, concentric remodeling in 31%, concentric hypertrophy in 19%, eccentric hypertrophy in 3% and adverse remodeling in only one patient (Figure 1).

Conclusions
In this group of patients with severe aortic stenosis, concentric hypertrophy was not the sole pattern of LV remodeling and two out of every five still presented a normal ventricular geometry and mass as assessed by CMR. LV response was dynamic after AVR which stands for complex and multifactorial interaction in these group of patients despite similar valvular pathophysiology and therapeutic intervention.

Funding Acknowledgement
Type of funding sources: None.
Effect of SLCO1B1 genotypes on statin intolerance and response to statins
Authors: Ghelani R , Davis L , Neves E , Khaled M , Khan T Z 
Published: October 2022

Abstract

Background
Statins are a cornerstone therapy for management of hypercholesterolaemia in primary and secondary prevention of cardiovascular disease, however there is individual variation regarding efficacy of therapy and adverse side-effects experienced.

Purpose
Polymorphisms of the SLCO1B1 gene have shown correlation with the risk of statin side-effects and efficacy of treatment, however in real-world clinical practice, their utility remains to be established.

Methods
We carried out retrospective multiple linear regression analysis using robust standard errors of 129 individuals undergoing genetic testing for the SLCO1B1 polymorphisms rs4149056 and rs2306283 to investigate for an association to statin side effects and efficacy respectively. In addition, logistic regressions which account for the binary nature of the outcomes were performed. The rs4149056 gene has 3 outcomes: T/T (considered least associated with statin intolerance), C/C (considered most associated with statin intolerance) and T/C (considered intermediately associated with statin intolerance). The rs2306283 gene has 3 outcomes: A/A (considered least associated with statin response), G/G (considered most associated with statin response) and A/G (considered intermediately associated with statin response).

Results
According to multiple regression and logistic regression analyses SLCO1B1 rs4149056 genotypes (C/C and T/C relative to the base type T/T) do not predict the incidence of myalgia, myopathy, creatine kinase rise, liver function derangement or gastrointestinal side effects at 5% significance. SLCO1B1 rs2306283 (G/G and A/G relative to the base type A/A) do not predict LDL response to statins (p-values 0.33 and 0.52 respectively).

Conclusions
The presence of rs4149056 C/C and T/C genotypes was not associated with an increased risk of statin side-effects. Similarly rs2306283 genotypes did not correlate with the efficacy of statin treatment. These genotype predictors were primarily based on Simvastatin – an earlier generation statin, whereas the majority of the patients in this cohort were treated with more contemporary and widely used statins such as Atorvastatin and Rosuvastatin. We therefore conclude that these genotypic markers may have limited application in modern day clinical practice and that substantial investment of limited resources towards them may not be justified.

Funding Acknowledgement
Type of funding sources: None.
Persistence to long-term PCSK9 inhibitors treatment and its effectiveness in familial hypercholesterolemia: data from the SAFEHEART study
Authors: Alonso R , Arroyo-Olivares R , Muniz-Grijalvo O , Diaz-Diaz J L , Sanchez Munoz-Torrero J , Zambon D , Fuentes-Jimenez F , Romero M J , Aguado R , Alvarez-Banos P , Manas M D , Arrieta F , Gonzalez-Bustos P , Argueso R , Mata P 
Published: October 2022

Abstract

Background
Most patients with heterozygous familial hypercholesterolemia (FH) do not achieve current LDL-C goals proposed by European guidelines with conventional lipid-lowering therapy (LLT). Chronic use of PCSK9 inhibitors (PCSK9i) have shown to reduce LDL-C levels up to 61% on top of statins. Persistence to chronic LLT is important to reduce the burden of atherosclerotic cardiovascular disease (ASCVD).

Purpose
To analyze persistence and effectiveness of PCSK9i in clinical practice setting in FH patients from the SAFEHEART register with long-term follow-up.

Methods
SAFEHEART is an open, long-term prospective study of a cohort of subjects with molecular diagnosis of FH. Follow-up is carried out every year through a standardized phone-call to collect clinical conditions, persistence to medications, lipid profile, and cardiovascular events. This study analyses subjects ≥18 years of age on stable LLT who have received PCSK9i.

Results
696 individuals (46% females), median age 56.4 years (IQR 49–66) started with PCSK9i (49% alirocumab and 51% evolocumab). Out of them 38% had history of ASCVD, and 89% were on maximum LLT. Median LDL-C at the moment of starting PCSK9i was 145 mg/dL (IQR, 123–177), representing a poor 2016 & 2019 ESC/EAS guidelines achievement (3% and 0.1% respectively). After a median follow-up of 3.7 years (IQR, 2.3–4.8), 669 patients (96%) remained on PCSK9i treatment during entire follow-up. Only 27 patients (4%) discontinued, 5 temporarily (0.7%) and 22 permanently (3.2%). Most common reasons for PCSK9i treatment interruption were medical decision (n=6), adverse event (AE) (n=5), patient decision not related with AE (n=5) and comorbidity (n=5). Median time to permanent discontinuation was 15 months (IQR, 4–33).
Median LDL-C levels observed and % of LDL-C reduction obtained after 1 year of treatment and in the last follow-up visit were: 63 mg/dL (IQR, 43–88), 61 mg/dL (IQR, 44–82), 57.6% (IQR, 39.5–69) and 58% (IQR, 44–68), respectively. 2016 ESC/EAS guidelines LDL-C goals was achieved by 70% of patients at year 1 and 77% in the last follow-up visit after the introduction of PCSK9i (p&lt;0.001). 2019 ESC/EAS goals were achieved by 44.5% and 48% (p=0.1).

Conclusion
Long-term persistence to PCSK9i treatment in FH patients is very high (96%) and reasons for discontinuation are diverse. This study shows that COVID-19 pandemic did not affected persistence to treatment. Effectiveness in LDL-C reduction and LDL-C goal achievement improved significantly with introduction of PCSK9i in clinical practice setting.

Funding Acknowledgement
Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): AMGEN
Simulation of bempedoic acid in the lipid-lowering treatment pathway using the European contemporary SANTORINI cohort of high- and very high-risk patients
Authors: Ray K K , Catapano A L , Diamand F , Wolowacz S , Haq I , Bilitou A 
Published: October 2022

Abstract

Background
Lowering LDL-C treatment goals in the 2019 ESC/EAS guidelines necessitates greater use of combination therapies (1). Cost of PCSK9 inhibitors (PCSK9i) and efficacy of ezetimibe alone as add on therapies limit population level achievement of LDL-C goals.

Purpose
This simulation study assessed the addition of oral bempedoic acid (BA) to ezetimibe in the treatment pathway in a real-world cohort of patients in order to assess the proportion of patients who might reach goal.

Methods
SANTORINI is a cohort study of European patients at high or very-high CV risk. Patients who were receiving any known LLT regimen with available data on LDL-C at baseline were eligible for this analysis. For patients not at risk-based LDL-C goals, the following treatment algorithm was applied (Figure 1), first the addition of ezetimibe and subsequently BA for those on statins, or addition of BA for those on ezetimibe and not at goal. Patients on PCSK9i remained in the cohort but no simulation was done. LDL-C reductions associated with ezetimibe and BA treatment were based on probabilistic distributions sourced from clinical trial efficacies based on prior studies (2–3). The effect of treatment on LDL-C levels was simulated through a Monte Carlo simulation run 10,000 times. No statin intensification was simulated as we assumed statin therapy was at maximum tolerated dose.

Results
At baseline (N=6252), mean age was 66 years and mean baseline LDL-C was 80.6 mg/dL with 1444 patients (23%) at goal; 93% (n=5797) were very high risk and 7% (n=455) high risk, of whom 84% (n=5227) were on statins, 23% (n=1447) on ezetimibe and 9% (n=546) on PCSK9i. Out of 4486 patients entering the simulation, 3419 received ezetimibe add-on with a third of those predicted to be achieving their risk-based goal (32%, n=1078/3419). Of those on ezetimibe and not at goal, the addition of BA would be predicted to result in another 36% goal achievement (n=1218/3408). Overall, the number of patients at goal would be expected to increase from 1444 (23%) at baseline to 2522 (40%) and 3740 (60%) after addition of ezetimibe and BA, sequentially. The mean LDL-C for the whole cohort would be expected to fall through this pathway from 80.6 mg/dL at baseline to 69.2 mg/dL and 61.1 mg/dL, respectively.

Conclusion
Few patients in the SANTORINI cohort were at goal at baseline and few would have LDL-C eligible for PCSK9i use. Optimising use of ezetimibe and BA after statins in the ESC/EAS 2019 LLT pathway could result in significantly more patients attaining lipid goals with likely additional health benefits.

Funding Acknowledgement
Type of funding sources: Private company. Main funding source(s): Daiichi Sankyo Europe GmbH
Worldwide comparative efficacy of nutraceuticals on lipid profile. an updated systematic review and network meta-analysis
Authors: Osadnik T , Golawski M , Lewandowski P , Morze J , Osadnik K , Pawlas N , Lejawa M , Jakubiak G , Mazur A , Schwingshackl L , Gasior M , Banach M 
Published: October 2022

Abstract

Introduction
In case of patients without indications to statin therapy, those being close to the target and especially with statin intolerance, nutraceuticals might be an additional option of hypercholesterolemia therapy. Despite a large number of nutraceuticals, little is known on their comparative efficacy due to the paucity of head-to-head comparisons. We aimed to assess the lipid-lowering effect of various nutraceuticals by means of network meta-analysis.

Methods
PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials were carefully searched to identify eligible studies to the meta-analysis. We included parallel or crossover randomized clinical trials (RCT), comparing head-to-head or to placebo/no intervention, the following nutraceuticals: a) artichoke, b) berberine, c) bergamot, d) garlic, e) green tea extract, f) plant sterols and stanols, g) policosanols, h) red yeast rice (RYR), i) silymarin, j) spirulina. We did not include soy protein, fiber, and lupin trials, as unlike other nutraceuticals they are in fact dietary interventions. Due to strikingly inconsistent results of policosanols RCTs carried out in Cuba and other countries, we excluded Cuban trials from main analysis.

Results
From the initially identified 4151 articles we finally included 131 studies. As some studies reported clinically different groups separately, they were split and finally we included 136 records, 134 with data on total cholesterol (TC), 125 with data on low-density cholesterol (LDL-C), 127 that provided information on high-density cholesterol (HDL-c) and 129 that included data regarding triglycerides (TG). Pooled studies covered data for 6755 patients randomized to nutraceutical arms and 6370 randomized to receive placebo/no intervention. For reducing TC bergamot, was identified as the most effective approach (P-score = 1.0) followed by RYR (0.90) and berberine (0.76). For increasing HDL-C, bergamot (0.98), berberine (0.85), and RYR (0.77) were the most effective. While evaluating LDL-C reduction, bergamot (1.00) and RYR (0.90) showed the highest reduction efficacy. Reducing effect of investigated nutraceuticals on TG levels was the highest for bergamot (1.00) and RYR (0.78). Majority of reports regarding Cuban policosanol trials implicated very high effectiveness of those nutraceuticals, which was in contrast to trials conducted in other countries

Conclusions
Bergamot, berberine, and RYR seemed to be most effective nutraceuticals in terms of lipid-lowering efficacy. Alleged high effectiveness of policosanols was not confirmed in our analysis. This analysis might support the physicians and patients' decisions to use only those nutraceuticals of confirmed efficacy.

Funding Acknowledgement
Type of funding sources: Public Institution(s). Main funding source(s): Medical University of Silesia, Katowice
Changes in smoking status after a cardiac rehabilitation program in Spain: description of a smoker's profile
Authors: Sestayo Fernandez M , Alonso Vazquez M , Gonzalez Maestro A , Gonzalez Salvado V , Diaz Balboa E , Neiro Rey M C , Gonzalez Juanatey J R , Pena Gil C 
Published: October 2022

Abstract

Background
Cigarette smoking is a major cardiovascular (CV) risk factor and aids to the development and progression of CV disease.

Purpose
To study the prevalence of smoking in a contemporary Spanish cardiac rehabilitation (CR) cohort, study changes in smoking status over time and define smoker's profile after CR.

Methods
Single-centre, observational retrospective study from all consecutive patients with ischaemic heart disease (n=1379, 6.6% women, age 65.78±11.02 years) that participated in a CR program from 2015 to 2020. Prevalence of smokers was studied over time, from CV event to 6 months after end of CR, including a stratified description of smokers per age group at CV event. Additionally, a comparative analysis of patient profile for those who continued smoking and patients that quitted smoking after CR, was performed.

Results
N=516 patients (37.4%) were active smokers at CV event, including 72 women (31% of all women) and 444 men (38.6% of all men). Highest percentage of smokers was distributed among the youngest age groups: with a 72.6% prevalence among those aged &lt;45 years and 57.9% among those aged 45–55 years. Smoking prevalence decreased with age. Also, there were less female than male smokers in all analysed age groups (Figure 1). At the beginning of CR, the global proportion of active smokers decreased significantly (p&lt;0.01) to a 15.3% (n=210) and continued to significantly decrease at end of CR (10%, n=124), maintaining similar levels at 6 months follow-up (9.9%, n=96). 58% of active smokers at CV event quitted smoking by end of CR. Ongoing smokers were significantly more (p&lt;0.05) depressed (n=20, 16.3%); and had significantly worse (p&lt;0.05) HADS scores at beginning of CR (anxiety: 6.49±3.98, depression: 5.41±4.46), Table 1.

Conclusions
Smoking is nowadays still highly prevalent among CR patients in our setting, especially among young men. Despite a significant fall in the prevalence of smokers after the end of the CR program, there is a non-negligible percentage of patients that keep smoking.
Targeted smoking cessation interventions should be aimed at smokers that have more depression and have worse HADS scores at baseline.

Funding Acknowledgement
Type of funding sources: None.
Altered platelet reactivity, coagulation, endothelial and inflammatory markers early after smoking cessation verified with cotinine plasma concentration
Authors: Ramotowski B , Undas A , Budaj A 
Published: October 2022

Abstract

Background/Introduction
Cigarette smoking is a potent modifiable risk factor for coronary artery disease (CAD) including patients after percutaneous coronary interventions (PCI). Cigarette smoking is associated with major changes in platelet, endothelial, inflammatory, and coagulation responses. The early period after PCI witnesses the highest risk of thrombotic events. However, data regarding alterations of prothrombotic state and platelet reactivity early after smoking cessation are scarce.

Purpose
We investigated alterations to platelet reactivity, coagulation and markers of platelet, endothelial and neutrophil activation in clopidogrel-treated patients with CAD after PCI before and after smoking cessation.

Methods
Patients aged 18 years or older, who smoked at least 10 cigarettes per day, at least 30 days after successful PCI with stent placement, and those treated with 75 mg clopidogrel and 75 mg acetylsalicylic acid (ASA) once daily, were included in the study and were encouraged to quit the habit. Platelet reactivity was measured with VerifyNow system and the concentrations of cotinine, thrombomodulin, P-selectin, platelet factor 4 (CXCL4/PF4), citrullinated histone H3 (H3cit), were assessed in blood samples at baseline and at the 30-day follow-up visit. Smoking cessation was defined as cotinine concentrations of &lt;50 ng/ml.

Results
Among 117 patients, being current smokers, who attended the baseline visit, 84 patients completed a 30-day follow-up. The median [interquartile range] age of patients was 50 [55–65] years, median body mass index was 27.55 [25.2–30.9] kg/m2, and a median load of smoking was 40 [30–47] pack-years. At the follow-up visit, 30 patients stopped smoking as confirmed by cotinine concentrations (study group) and 54 patients continued smoking (control group). Baseline characteristics were similar in both groups. In the study group as compared to the control group, at day 30 a change in platelet reactivity was larger (Δ platelet reactivity units (PRU) 19 [2, 43] vs −6 [−32, 37], p=0.018), along with a change in P-selectin concentration (−11.82 [−23.62, 1.34] vs 7.19 [−14.24, 17.19] ng/ml), p=0.005). The change in the concentrations of thrombomodulin, CXCL4/PF4, and citH3 did not differ significantly between groups.

Conclusion
In the early period after smoking cessation in coronary artery disease patients following PCI treated with clopidogrel and ASA, an increase in platelet reactivity with a decrease in P-selectin levels was observed. No significant changes in other markers were noticed. It might be speculated that the risk of thrombotic complications might be paradoxically enhanced among such patients after smoking cessation despite dual antiplatelet therapy.

Funding Acknowledgement
Type of funding sources: Public Institution(s). Main funding source(s): Centre of Postgraduate Medical Education