bluuebunny/crossref_metadata_2025_split huggingface dataset:
AI-enhanced detection of coronary inflammation predicts 10-year risk for cardiac mortality and MACE in individuals with no or minimal coronary atherosclerosis on routine CCTA
Authors: Chan K , Wahome E , Nicol E , Mittal T K , Petersen S E , Pugliese F , Adlam D , Desai M , Patel P , Tomlins P , Neubauer S , Channon K M , Blankstein R , Deanfield J , Antoniades C 
Published: October 2024

Abstract

Background
Coronary CT angiogram (CCTA) is one of the first line investigations for patients with chest pain suspected of coronary artery disease (CAD). Current CCTA interpretations mainly focus on luminal obstruction, which is identified in the minority of patients, whereas the majority who have no or minimal atherosclerotic plaques visible on CCTA are often provided with reassurance. However, residual risk from inflammation that drives atherosclerosis and plaque vulnerability are not captured with luminal stenoses alone. Fat attenuation index (FAI) Score quantifies coronary inflammation on routine CCTA, and integrate with clinical risk factors/plaque burden in an artificial intelligence enabled risk algorithm (AI-Risk) that could help to risk stratify this patient group.

Purpose
To evaluate the prognostic value or FAI Score and AI-Risk in the risk stratification of patients with no or minimal atherosclerosis.

Methods
In a nested cohort within the Oxford Risk Factors and Non-invasive imaging (ORFAN) study, consecutive patients (n=3,393) who underwent routine clinical CCTA were followed up over a median(IQR) 7.7(6.4-9.1) years for cardiac mortality and major adverse cardiac events (MACE, including myocardial infarction, new onset heart failure, cardiac mortality). CADRADS 2.0 classification 0 or 1 were used to define no or minimal luminal stenoses. FAI Score was calculated for each of the 3 epicardial coronary arteries.

Results
A total of 1,678 patients had no or minimal atherosclerosis on CCTA [median (IQR) age 53(45-63), 49.8% male]. Cardiac mortality occurred in 3.1% and MACE occurred in 8.8% of the patients during the follow-up period. Patients at the lowest quartile of FAI Score or low/medium AI-Risk classification showed very low event rate during follow up. Patients with the highest quartile of LAD FAI Score showed 9 times higher risk of cardiac mortality (Panel A) and 5 times higher risk of MACE (Panel B) compared to those at lowest quartile. Similar findings were observed for LCX and RCA. Finally, integrating coronary inflammation with clinical risk factors and plaque burden, patients at very high AI-Risk classification showed 5 times higher risk of cardiac mortality (Panel C), and 4 times higher risk of MACE (Panel D) compared to those with low/medium risk classification.

Conclusion
Coronary artery inflammation measured by FAI Score could stratify the risk of patients with no or minimal coronary atherosclerosis on CCTA, and could help to guide early preventative treatments.
Outcomes of post-acute coronary syndrome patients enrolled in a phase 2 cardiac rehabilitation program
Authors: Moreira M , Frias D , Schmidt C , Alves Dias V , Magalhaes S , Santos M , Torres S 
Published: October 2024

Abstract

Introduction
Cardiac rehabilitation (CR) is a class I recommendation in the management of patients with acute coronary syndrome (ACS), namely ST-elevation myocardial infarction (STEMI) and non-ST acute coronary syndrome (NST-ACS). Reported mortality and recurrent cardiovascular (CV) events are still unacceptably high in these patients.

Purpose
To assess CV outcomes of patients enrolled in a CR program and its association with ACS presentation.

Methods
Single-center, retrospective observational study that included all consecutive post-ACS patients enrolled in a phase 2 CR program in 2017, with a follow-up of 24 months. Group 1 were patients with STEMI; group 2 were patients with NST-ACS. Major adverse cardiovascular events (MACE) were defined as a composite of death, non-fatal ACS, non-fatal stroke, and unplanned revascularization.

Results
Of the 202 ACS patients who attended the CR program in 2017, 4 were excluded due to missing data. Of the 198 patients analyzed (age 60.3±10.7 years, 82% male), 101 patients had a STEMI and 97 NST-ACS. STEMI patients were significantly younger (57±9.5 vs. 63±10, p&lt;0.001), with fewer CV risk factors (diabetes 16% vs. 32%, p=0.008; hypertension 51% vs. 72%, p=0.002; obesity 17% vs. 31%, p=0.020; dyslipidemia 54% vs. 77%, p&lt;0.001), except for active smoking (53% vs. 29%, p=0.001), and were less likely to have previous history of coronary artery disease (9% vs. 31%, p&lt;0.001). During the 3-month CR program, both groups achieved significant reduction in body mass index, LDL-Cholesterol, functional capacity, and smoking cessation rates. At 3-, 12-, and 24-months evaluation, both groups showed no differences in risk factor management, nor differences in lipid-lowering therapy, namely percentage of high-intensity statin and ezetimibe use. STEMI patients were treated more frequently with ticagrelor (86% vs. 67%, p=0.001) at baseline. MACE occurrence was significantly lower in STEMI patients (11% vs. 28%, p=0.003), driven mainly by recurrent ACS (4% vs. 15%, p=0.006).

Conclusions
In our study, NST-ACS patients had significantly higher CV disease burden and worse outcomes at 24-month follow-up. Despite the heightened CV risk in this group, secondary prevention treatment intensity was similar in both groups.
Efficacy of lipid lowering therapy beyond statins to prevent cardiovascular events
Authors: Dykun I , Khoury M , Rassaf T , Mahabadi A A 
Published: October 2024

Abstract

Background
Lipid lowering therapy is a key cornerstone in secondary prevention of patients with coronary artery disease. However, only a minority of patients with statin therapy reach LDL thresholds as suggested by the ESC. Ezetimibe, bempedoic acic, and proprotein convertase subtilisin/kexin type 9 (PCSK-9) (synthase-) inhibitors allow for the reduction in LDL-cholesterol in addition to statin therapy.

Purpose
We aimed to perform a meta-analysis of existing trials, evaluating how lipid lowering therapy beyond statins impacts cardiovascular outcome. In specific, we evaluated the potential influence of duration of follow-up on the association with mortality endpoints.

Methods
We performed a systematic search using the Pubmed, Cochrane, SCOPUS, and Web of Science databases for studies, evaluating the impact of an intensified lipid lowering therapy via ezetimibe, bempedoic acid, Bococizumab, Alirocumab, Evolocumab, Inclisiran in addition to statin therapy compared to statin therapy alone. Manuscript and congress presentations, published until 1st of August 2023, were included. We made our search specific and sensitive using Medical Subject
Headings terms and free text and considered studies published in English language. Search terms used were : "Bempedoic Acid" or "Bococizumab" or "Alirocumab" or "Evolocumab" or "Ezetimibe" or "Inclisiran" and "statin" and "cardiovascular events".

Results
A total of 123,785 patients from 15 randomized controlled trials (IMPROVE-IT, FOURIER, ODYSSEY Outcomes, ODYSSEY LONG TERM, EWTOPIA 75, PACMAN-AMI, RACING, SIPRE I, SPIRE II, OSLER-1 and OSLER-2, CLEAR HARMONY, CLEAR OUTCOMES, CLEAR SERENITY, CLEAR WISDOM) were included. Treatment with ezetimibe or a PCSK-9 inhibitor was associated with a 19% risk reduction in cardiovascular events (OR [95%CI]: 0.81 [0.75; 0.86]). Effect sizes were similar for myocardial infarction (0.81 [0.74; 0.89]) and even more pronounced for ischemic stroke (0.77 [0.70; 0.84]). In contrast, all-cause mortality was not improved by the intensified lipid lowering therapy (0.99 [0.93; 1.04]). Stratifying by follow-up duration of &lt; vs. ≥ 3 years, no improvement in all-cause mortality was observed in both groups (&lt;3 years: 1.04 [0.93; 1.17]; ≥3 years: 0.97 (0.88; 1.06). No relevant heterogeneity and inconsistency between groups was present in all analyses (detailed data not shown).

Conclusion
Intensified LDL-lowering therapy with ezetimibe, bempedoic acic or PCSK-9 inhibitors, in addition to statins, reduces the risk of myocardial infarction and stroke, however, does not impact overall mortality. A potential survival benefit was also not observed in studies with follow-up duration of ≥ 3 years.
Changes in lipid lowering therapy one year after percutaneous coronary intervention: data from the large contemporary ZON-HR registry
Authors: Peeters D A M , Janssen S , Woelders E C I , Winkler P J C , Damman P , Luijkx J J P , Remkes W S , Van 'T Hof A W J , Van Geuns R J M 
Published: October 2024

Abstract

Background
Patients who underwent percutaneous coronary intervention (PCI) should receive at least high-intensity statin therapy according to current ESC guidelines to prevent ischemic events. However, previous studies have shown that about 80% of the patients using high-intensity statin monotherapy are not reaching the low density lipoprotein- cholesterol (LDL-C) target value of below 1.4 mmol/L. This means that additional lipid lowering therapy is necessary in most patients. The ‘Zuid-Oost Netherlands Heart Registry’ (ZON-HR) is a multicentre, prospective registry designed to improve secondary prevention after PCI by a patient-tailored approach.

Purpose
To describe changes in lipid lowering therapy one year after PCI in the ZON-HR.

Methods
Since November 2020 data from all patients who underwent PCI in one of the four participating ZON-HR hospitals were included. In 4811 patients one year follow-up was completed. Patients with known discharge medication and medication at one year after PCI were included in the analyses (n=3487). Combination therapy was defined as having at least two different lipid lowering medications prescribed. The association between predefined variables and combination therapy at one year post PCI was assessed with multivariable logistic regression to adjust for baseline differences.

Results
The mean age of the patients was 67.7 ± 10.7 years, 72.4% was male and the baseline LDL-C value was 2.7 ± 1.1 mmol/L. While patients with an acute coronary syndrome (ACS) had higher LDL-C values at baseline, they received combination of lipid lowering therapy at discharge less often compared to patients with a chronic coronary syndrome (CCS) (7.9% vs 11.5%, p&lt;0.001) (table 1). After one year, both ACS and CCS patients were treated more often with combination therapy (20.1% vs 23.3%, p=0.047). However, still only about 20% of the patients were receiving combination therapy one year after PCI. In the ACS population, younger patients with higher LDL-C values at baseline and previous myocardial infarction had a higher chance of receiving combination lipid lowering therapy one year after PCI (table 2).

Conclusion
Additional lipid lowering medication is needed, besides high-intensity statins, in order to reach the strict LDL-C target values in very high risk patients. However, the step-up from mono- to combination lipid lowering therapy only occurs in about 10% of the patients. Lipid lowering combination therapy is prescribed more often in CCS patients compared to ACS patients, both at discharge and one year after PCI.Baseline values and combination therapyPredictors combination therapy at 1 year
Modifying effect of obesity status on the association between low-density lipoprotein cholesterol with incident hemorrhagic stroke: evidence from a community-based longitudinal cohort study in China
Authors: Zhang L , Luo X Y , Liu Y K , Fan F F , Zheng B , Zhang Y , Li J P 
Published: October 2024

Abstract

Background
Previous results on the association between lipids and hemorrhagic stroke were controversial. Modifying effect of obesity on the association between low-density lipoprotein cholesterol (LDL-C) and hemorrhagic stroke risk in the Chinese community-based population remains unclear.

Objectives
We aimed to investigate the association between LDL-C and hemorrhagic stroke risk in the Chinese community-based population. In addition, we aimed to explore the potential modifying effect of obesity status, particularly abdominal obesity, on this relationship.

Methods
A total of 7899 eligible subjects, without history of stroke and myocardial infarction, and any use of lipid-lowering medication at baseline, were enrolled in this study. Levels of LDL-C, total cholesterol (TC), triglyceride (TG), and high-density lipoprotein cholesterol (HDL-C) were assessed at baseline. The primary endpoint was the hemorrhagic stroke. Abdominal obesity was defined as waist circumference &gt; 90 cm in men and &gt; 85 cm in women.

Results
Of all participants, the mean age was 56.13 ± 8.87 years, 2848 (36.1%) were male. During a mean 9.71-year follow-up, 66 hemorrhagic strokes occurred. After multivariable adjustment (Figure 1), compared to participants with LDL-C levels 2.6 – 3.4 mmol/L, those with LDL-C levels &lt; 1.8 mmol/L had 3.32 times the risk (hazard ratio [HR]: 3.32; 95% confidence interval [CI]: 1.24, 8.84) of incident hemorrhagic stroke. Compared with participants with TC levels 3.1 – 5.2 mmol/L, HR (95% CI) was 7.82 (2.36, 25.90) for hemorrhagic stroke in those with TC &lt; 3.1 mmol/L. We observed no significant associations between TG or HDL-C levels and hemorrhagic stroke risk. Interaction effects were found between obesity and LDL-C for incident hemorrhagic stroke. Accordingly, significant associations between low LDL-C level (&lt; 1.8 mmol/L) and the risk of incident hemorrhagic stroke were found only among abdominal obesity participants (HR: 3.76; 95% CI: 1.01, 13.97), or those with body mass index (BMI) &gt; = 24 kg/m2 (HR: 3.74; 95% CI: 1.24, 11.34) (Figure 2).

Conclusions
LDL-C levels &lt; 1.8mmol/L and TC levels &lt; 3.1mmol/L were associated with increased risk of hemorrhagic stroke. Modifying effect of obesity status on the association between low LDL-C level and hemorrhagic stroke was observed in our study.
Cardiovascular events in patients treated with bempedoic acid vs. placebo: systematic review and meta-analysis
Authors: Mutschlechner D , Tscharre M , Huber K , Gremmel T 
Published: October 2024

Abstract

Aims
Reduction of low-density lipoprotein cholesterol (LDL-C) decreases cardiovascular mortality and morbidity. Bempedoic acid represents a promising novel lipid modifying agent for patients who cannot reach guideline recommended LDL-C goals or statin-intolerant patients, but data on safety and cardiovascular outcomes are limited. We therefore aimed to systematically review randomized controlled trials investigating bempedoic acid versus placebo in patients with hyperlipidemia.

Methods
A systematic search on the databases PubMed, Web of Science, and Embase until 20 March 2023 was performed. All randomized trials comparing bempedoic acid (180 mg daily) with placebo in patients with an indication for lipid-lowering therapy were included. As primary endpoint we analysed three-point major adverse cardiovascular events (MACE) consisting of cardiovascular death, non-fatal myocardial infarction (MI) or non-fatal stroke. The analysis was carried out using the odds ratio as the outcome measure. Due to the expected heterogeneity across studies a random-effects model was fitted to the data.

Results
Out of 258 manuscripts, 10 manuscripts fulfilled the inclusion criteria. In total, these trials included 18,200 patients (9,765 on bempedoic acid, 8,435 on placebo). Bempedoic acid significantly reduced MACE compared to placebo (OR 0.84 [95% CI 0.76-0.96]; p&lt;0.001; I2=0%). The endpoint reduction was driven by a lower rate of non-fatal MI, whereas bempedoic acid had no significant effect on stroke (OR 0.86 [95% CI 0.69-1.08]; p=0.20, I2=0%) and all-cause mortality (OR 1.19 [95% CI 0.73-1.93]; p=0.49; I2=18%).

Conclusion
Bempedoic acid reduced non-fatal MI in patients with hyperlipidemia, whereas it had no significant effect on stroke and all-cause mortality.Figure.Forest plot for three-point MACE
Association of lipid target achievement and cardiovascular outcomes following statin initiation: a population-based cohort study
Authors: Thompson W , Jeong I , Basque S , Abdel-Qadir H , Austin P C , Ko D T , Famiyeh I , Chu A , Fang J , Odutayo A , Jackevicius C , Godoy L C , Lee D S , Udell J A 
Published: October 2024

Abstract

Introduction
Non-high density lipoprotein cholesterol (non-HDL-C) is increasingly incorporated into clinical practice guidelines along with low density lipoprotein cholesterol (LDL-C) to guide lipid-lowering therapy decisions. We aimed to examine patterns of LDL-C and non-HDL-C levels after statin initiation for primary prevention of cardiovascular disease (CVD), and their association with incident CV events.

Methods
We conducted a population-based cohort study of Ontario, Canada residents age ≥66 years who initiated a statin for primary prevention between January 1, 2012 and December 31, 2019. For those surviving 1-year after statin initiation, we determined the proportion with a lipid panel in the 1-year period after a statin was started. For those with a lipid panel, we used the lipid panel closest to the end of the 1-year period to categorize individuals based on the LDL-C and non-HDL-C thresholds in the 2021 Canadian Cardiovascular Society dyslipidemia guidelines (Table 1). We stratified by diabetes/chronic kidney disease (CKD) status. We evaluated the association between LDL-C/non-HDL-C category and a composite of all-cause mortality or hospitalization for myocardial infarction, stroke or revascularization (primary outcome). We also investigated the association between each category and each component of the primary outcome. The index date was the 365 days after a statin was initiated and follow-up was until December 31, 2020. We used a cause-specific hazards model for analysis, adjusted for clinical and sociodemographic confounders.

Results
Our cohort comprised 173,127 people. In the 1-year period after statin initiation, 72% of people had a follow-up lipid panel performed. Median follow-up after that was 2.5 years. Compared with those meeting both LDL-C and non-HDL-C targets, being above both targets was associated with an increased rate of the primary outcome for people without diabetes/CKD (HR 1.10, 95% CI 1.05 to 1.15) and those with diabetes/CKD (HR 1.16, 95% CI 1.09 to 1.23). Being at LDL-C target but above non-HDL-C target was associated with an increased rate of the primary outcome for people with diabetes/CKD (HR 1.16, 95% CI 1.03 to 1.30) but not for those without diabetes/CKD (HR 1.05, 95% CI 0.93 to 1.17).

Conclusions
In this population-based cohort, having an LDL-C and non-HDL-C above guideline-recommended targets after statin initiation was associated with an increased rate of adverse outcomes. These findings support the residual risk associated with incompletely controlled LDL-C or non-HDL-C levels after initiating statin therapy for primary prevention.Primary outcome associationsComponents of primary outcome
Sex differences in reporting of statin-associated diabetes mellitus to the US Food and Drug Administration
Authors: Leyba K , Martin J M , Aquilante C A , Shalowitz E S , Kudron E K , Reusch J E B R , Regensteiner J G R , Kao D P K 
Published: October 2024

Abstract

Background
Statins have been reported to precipitate diabetes mellitus (DM) in some patients. Limited evidence suggests that this occurs in women more frequently than men, but direct comparisons of rates of reporting of statin-associated DM between men and women are lacking.

Purpose
To determine whether there are sex-specific differences in post-marketing reporting of statin-associated DM.

Methods
We conducted a retrospective pharmacovigilance analysis of spontaneously reported adverse drug events (ADEs) submitted to the Food and Drug Administration (FDA) Adverse Event Reporting System between January 1997 and September 2023. A Proportional Reporting Ratio (PRR) was used to identify the rate of reported statin-associated DM ADEs relative to the rate of DM ADEs reported with all other medications. We compared signals of disproportionate reporting (SDRs) between men and women using a modified relative odds ratio (ROR).

Results
During the study period, there were two-fold as many reports of statin-associated DM in women than in men (14,793 versus 7,307, respectively), despite the fact there were only 7% more non-DM statin ADEs reported in women compared to men (512,134 versus 480,849, respectively). Compared to the background rate of reporting for all ADEs (0.6%), statin-induced DM was disproportionally reported for all subjects in aggregate (2.1%, PRR=3.7) as well as for men only (1.5%, PRR=2.4) and for women only (2.9%, PRR=5.3). Significant PRRs for DM were observed with each statin and for all statins collectively (Figure 1). Statins were reported as the primary- or secondary-suspected cause of DM in women with considerably greater frequency than in men (58% versus 29%, respectively). Rates of reporting of statin-associated DM were higher in women than in men for all statins, with the greatest difference being observed with atorvastatin (ROR 3.0), and the lowest difference being observed with rosuvastatin (ROR 1.2) (Figure 1).

Conclusions
Post-marketing ADE surveillance data suggest a markedly higher rate of incident DM associated with statins than with other medications and a higher rate of reporting of statin-associated DM in women than in men. Future studies should consider sex-moderated mechanisms of statin-associated DM.Figure 1
Association of obesity and metabolic health status with cerebral small vessel disease in stroke-free individuals
Authors: Ishida A , Nakanishi R , Miyagi T , Yamazato M , Ohya Y , Kusunose K 
Published: October 2024

Abstract

Background
It remains unclear whether obesity itself or metabolic abnormalities coexisting with obesity, are associated with stroke.

Purpose
We aimed to investigate the association of obesity and metabolic health status with cerebral small vessel disease (SVD) in stroke-free participants from a brain health check-up.

Methods
We conducted a cross-sectional study of 6088 stroke-free participants who underwent brain magnetic resonance imaging at a brain check-up between 2013 and 2020. Participants were categorised according to sex-specific waist circumference and metabolic health status. A metabolically healthy status was defined as the absence of components of metabolic syndrome other than a large waist circumference, such as high blood pressure, hyperglycaemia, and dyslipidaemia. The total SVD score was derived from four magnetic resonance imaging markers: silent lacunar infarcts, cerebral microbleeds, moderate-to-severe white matter hyperintensities, and enlarged perivascular spaces.

Results
The mean age of the participants was 55±12 years and 46% were women. The prevalence of metabolically healthy obesity was 650 (11%) and the proportion of metabolically healthy obesity among individuals with obesity was 24%. The prevalence of metabolically unhealthy obesity was 2043 (34%), and the proportion of metabolically unhealthy obesity among individuals with metabolically unhealthy individuals was 58%. The prevalence of moderate-to-severe SVD scores (≥2) was 348 (6%), which was higher in metabolically unhealthy individuals, regardless of obesity status. Compared with the metabolically healthy non-obesity group, the metabolically unhealthy non-obesity (odds ratio 2.22 [95% CI, 1.44–3.42]) and metabolically unhealthy obesity (odds ratio, 2.76 [95% CI, 1.80–4.24]) groups had a significantly higher multivariable-adjusted risk for a total SVD score of ≥2. Further sensitivity analyses using BMI-defined obesity instead of waist circumference-defined obesity yielded similar results.

Conclusions
Abdominal and general obesity alone are not associated with higher total SVD scores in stroke-free individuals. Unhealthy metabolic components, especially high blood pressure and hyperglycaemia, are important risk factors for SVD.