bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deciphering lipoprotein(a) atherogenicity with use of high-throughput proteomics
Authors: Morze J , Marston N A , Melloni G E M , Da Silva G R , Rynkiewicz A , Wittenbecher C 
Published: October 2024

Abstract

Background
Accumulating observational and genetic evidence suggests that lipoprotein(a) [Lp(a)], is significantly more atherogenic than other apolipoprotein-B containing particles. Systemic inflammation is thought to mediate the atherogenic effects of Lp(a). Previous studies have predominantly focused on single inflammatory biomarkers, an approach that fails to capture the broader molecular response to elevated Lp(a) levels.

Purpose
The aim of this study was to derive a proteome-wide signature of plasma Lp(a) concentrations and subsequently identify the pathways through which Lp(a) influences the risk of coronary artery disease (CAD).

Methods
This study included 41,123 UK Biobank participants with baseline Lp(a) measurements who also underwent a proteomic assessment. Relative concentration of 2,920 proteins was quantified in EDTA plasma samples using a high-throughput proximity extension assay. Lp(a)-associated proteins were identified in linear regression models, adjusting for age, sex, body mass index, race, smoking status, estimated glomerular filtration rate, medication use, and apolipoprotein B. Proteins linked with Lp(a) concentration were then evaluated for their association with incident CAD risk using Cox proportional hazards models. Significant traits were further included in pathway enrichment analysis.

Results
Out of 2,920 analyzed proteins (Figure 1), 140 showed a positive association with Lp(a) concentration, while 336 exhibited a negative association after adjustment for multiple testing (False discovery rate &lt; 0.05). The strongest positive associations were observed for apolipoprotein F, group 10 secretory phospholipase A, and C4b-binding protein beta chain. The strongest negative associations were observed for asporin, aminoacylase-1, and retinol-binding protein 5. Among 140 proteins positively associated with Lp(a), 49 were associated with an increased risk of CAD. Conversely, among the 336 proteins negatively associated with Lp(a), 10 were associated with a decreased risk of CAD. Pathway enrichment analysis (Figure 2) indicated that proteins linked with both Lp(a) levels and CAD risk predominantly upregulated pathways related to peptide-ligand receptor signalling, platelet degranulation, neutrophil degranulation, and cytosolic calcium response. Conversely, pathways related to HDL remodeling, PI3K/AKT, KIT, and nuclear receptor signalling were downregulated.

Conclusions
The greater atherogenic potential of Lp(a) may be attributable to the modulation of several molecular pathways, particularly those involving platelet and neutrophil responses, cell signalling, and lipoprotein metabolism.
Sex differences in secondary prevention and outcomes post-myocardial infarction in Scotland
Authors: Pana T , Mamas M A , Myint P K , Dawson D 
Published: October 2024

Abstract

Background
Sex differences in outcomes after myocardial infarction (MI) are of increasing interest. Differential receipt of evidence-based treatments may contribute to such disparities.

Purpose
In this study, we investigate sex differences in the burden of risk factors, in-hospital and long-term treatment and outcomes in contemporary practice in Scotland, by analysing a nationwide sample of consecutive MI admissions.

Methods
All MI admissions centrally recorded between 2010-2016 by Public Health Scotland were included and followed up until the end of 2021. Poisson regressions analysed in-hospital outcomes (percutaneous coronary intervention (PCI), mortality and post-discharge secondary prevention medication). Models were adjusted for age, co-morbidities and ST-elevation on the electrocardiogram. Royston-Parmar models analysed long-term outcomes (all-cause and cardiovascular mortality, major adverse cardiovascular events (MACE)) and were sequentially adjusted for confounders (age, comorbidities, secondary prevention medications). A 2:1 age and sex-matched general population were included as controls.

Results
Of a total 47,063 MI patients, 15,776 (33.5%) were women. They were matched with 81,641 controls free of major cardiovascular disease. Median (interquartile range) age was 64 (56-72) years for men and 69 (60-75) years for women. Obesity, hypertension and renal disease were the risk factors more prevalent amongst women, while men had higher rates of previous MI, peripheral vascular disease and atrial fibrillation. Compared to men, women were less likely to undergo PCI (risk ratio (95% confidence interval) – 0.87 (0.86-0.89)) or receive secondary prevention (0.94 (0.93-0.95)), but had similar in-hospital mortality (1.06 (0.99-1.13)), after multi-variable adjustment. Over a median follow-up of 8.4 (6.8-10.2) years, women had higher raw rates of adverse outcomes. However, after full confounder adjustment, this translated into lower risk for women of all cause-mortality 0.92 (0.89-0.95), cardiovascular mortality 0.82 (0.78-0.87) and MACE 0.92 (0.88-0.95) (Figure 1). The female survival advantage was attenuated post-MI in comparison to controls free of significant cardiovascular disease (Figure 2).

Conclusions
Women and men have different MI risk factor profiles. Women had overall worse crude outcome rates after MI, driven by age and comorbidities. This may have been driven further by undertreatment after MI, including PCI and secondary prevention. Urgent identification of drivers for such disparities in care is warranted in order to improve outcomes and ensure health equity.
Beyond secondary prevention drugs: added benefit in survival and events of a healthy lifestyle in patients after an acute coronary syndrome
Authors: Canovas Rodriguez E C , Kallmeyer A K , Tarin N T , Cristobal C C , Huelmos A H , Pello A P , Acena A A , Gutierrez Landaluce C G , Gonzalez Lorenzo O G , Lumpuy Castillo J L , Alonso J A , Lopez Bescos L L , Lorenzo O L , Blanco Colio L B C , Tunon J T 
Published: October 2024

Abstract

Background
Despite advances in drug treatment and secondary prevention programs, cardiovascular disease remains the leading cause of death. The full extent and independent benefit of a healthy lifestyle, particularly after optimal medical therapy in secondary prevention, has not been widely reported.

Purpose
To quantify the added benefit on survival and events of a healthy lifestyle following an acute coronary syndrome (ACS). Our study seeks to answer the question: Is adherence to medical therapy sufficient or a healthy lifestyle provides additional improvement?.

Methods
This a prospective observational multi-center study of 685 patients included during admission for ACS. At 6 months patients were asked about their post-ACS lifestyle and were given a score (range: 0-7) with the following items: Intake of ≥3 fruits and vegetables/day, ≥2 fish servings/week, ≤7 alcohol beverages/week, feeling stress RESULTS: After adjusting for demographic variables, cardiovascular risk factors, characteristics of the index event, high-sensitivity C-reactive protein (hs-CRP), and drug therapy, multivariate Cox regression showed that the lifestyle SCORE was independently and inversely associated with both the incidence of the primary outcome (ischemic events [any ACS, stroke, or Transient Ischemic Attack] or death) (HR 0.65 (CI95% 0.44-0.96); p=0.029) and death (HR 0.41 [95%CI 0.18-0.91]; p=0.029). Statin therapy was also independently and inversely associated with both the incidence of the primary outcome. Kaplan-Meier curves showed a higher event-free survival for both outcomes in patients with SCORE≥4 than in those with SCORE&lt;4 (p=0.03 and p&lt;0.001, respectively). Additionally, patients with a SCORE≥4 had a significantly greater decrease of total cholesterol (-52 [-16.5, -79] vs -38 [-7.5, -68] mg/dl; p=0.040) and hs-CRP (-1.1 [-0.1, 2.5] vs -0.5 [0.7, -1.9] mg/L; p=0.001) at six months.

Conclusions
Among patients with ACS and similar medical therapy, a healthy lifestyle is an independent and added marker of a lower incidence of ischemic events and death. It is also associated with a better lipid profile and lower inflammation.
National dispensing of evidence-based treatment for New Zealand patients before and after peripheral arterial or percutaneous coronary procedures; undertreatment in plain sight
Authors: Wells S , Zhao J , Choi Y , Poppe K , Jackson R , Kerr A 
Published: October 2024

Abstract

Background/Introduction
Cardiovascular management guidelines recommend that those undergoing arterial procedures for atherosclerotic disease should be on a long-term antithrombotic agent, statin and blood pressure (BP) lowering (triple therapy) to prevent or delay future ischaemic events or death. Internationally, treatment gaps have been reported for people having peripheral arterial disease (PAD) procedures.

Purpose
We aimed to investigate national rates of triple therapy dispensing before and after admission for a percutaneous coronary intervention (PCI) compared to a PAD procedure.

Methods
All people aged 18-84 years admitted for a publicly-funded PCI or PAD procedure in New Zealand between 1 January 2015 and 30 June 2020 were identified. Data were linked to national community dispensing records for antithrombotic agents, statins and BP lowering and the adjusted relative risk (adjRR) of dispensing individual medication classes and triple therapy investigated 6 months prior-procedure and 0-6 months and 7-12 months post-procedure. Analyses were controlled for age, sex, prioritised ethnicity, socioeconomic deprivation index, diabetes and prior cardiovascular disease.

Results
During the study period, 26,383 people were admitted for a PCI procedure and 10,938 people for PAD. Compared to PCI, those with PAD were more likely to be women, older (median age 69 vs 66 years), of Māori or Pacific ethnicity, living in more deprived communities, more likely to have diabetes (33% vs 24%) and a prior admission for cardiovascular disease (63% vs 52%). Triple therapy in the 6 months prior to procedure was 48% for PAD compared to 37% for PCI (adjRR 1.04; 1.03-1.05); however, in the 6 months post-discharge, improved for PCI more than PAD (PAD 58% vs PCI 91%, [adjRR 0.82; 0.81-0,83]) with decreased dispensing in both cohorts by 7-12 months post procedure (PAD 55% vs PCI 83%, [adjRR 0.84; 0.83-0,84]).

Conclusions
Patients undergoing atherosclerotic arterial procedures are at high risk of future fatal and nonfatal cardiovascular events. Less than half the patients who were admitted for a PCI or PAD procedure had been dispensed triple therapy in the 6 months prior to admission. Post procedure, 91% of PCI patients were on triple therapy but this substantial increase did not occur for PAD patients. The risk management gap for those who have peripheral arterial compared to coronary procedures indicates clear clinical and system-related deficiencies and a national quality improvement approach is required to address these issues.
Figure 1. Adjusted relative risk of being dispensed preventive medications for patients who had a PAD procedure, compared to patients who had a PCI procedure [after adjusting for age, sex, ethnicity, NZDep, history of CHD (including prior PCI and CABG), stroke/TIA, haemorrhagic stroke, heart failure, PVD, and diabetes]
Impact of the severe familial hypercholesterolemia status on atherosclerotic risks
Authors: Tada H , Kojima N , Takeji Y , Nohara A , Kawashiri M , Takamura M 
Published: October 2024

Abstract

Backgrounds
Risks of atherosclerotic events substantially vary even among patients with familial hypercholesterolemia (FH) with extremely high risk based on life-long exposure to high low-density lipoprotein cholesterol levels.

Purpose
This study aimed to examine the impact of the severe FH status defined by the International Atherosclerosis Society (IAS).

Methods
Data of patients with FH (N = 1,050, male = 490) who were admitted to our university hospital between 2000 and 2020 and who were followed up were retrospectively reviewed. The number of major adverse cardiac events (MACEs), including mortality associated with cardiovascular disease, acute coronary syndrome, and ischemic heart disease requiring coronary revascularization per 1,000 person-years, was calculated. Hazard ratio was also calculated using Cox proportional model.

Results
Overall, 545 (51.9%) patients had severe FH. The median follow-up duration was 12.6 years. In total, 171 MACEs were recorded during the follow-up period. Severe FH was significantly associated with MACE (hazard ratio = 6.48, 95% confidence interval = 2.56–10.40, P &lt; 0.001). The event rates per 1,000 person-years in the primary prevention group of non-severe FH and severe FH, were 0.0 and 15.6, respectively. The event rates per 1,000 person-years in the secondary prevention group of non-severe FH and severe FH, were 2.0 and 32.3, respectively.

Conclusions
Patients with severe FH exhibited significantly higher risks in primary and secondary prevention settings. This simple criterion provides useful information for identifying patients with even higher risk who may need further management.
Usefulness of visual classification for cardiac pathophysiology using count-washout rate map in iodine-123-beta-methyl-P-iodophenyl-pentadecanoic acid scintigraphy
Authors: Ono R , Miyauchi H , Iimori T , Hoshi K , Kobayashi Y 
Published: October 2024

Abstract

Background
Myocardial washout rate (WR) analysis of radiopharmaceuticals is utilized in nuclear cardiology to evaluate the clinical pathophysiology of the heart. WR is defined as the ratio of the difference between the counts in the early image and time-decay-corrected delayed image divided by the former. The myocardial WR of iodine-123-β-methyl iodophenyl-pentadecanoic acid (BMIPP) is an indicator of myocardial lipolysis, and a decreased WR (&lt;10%) of BMIPP is one of the diagnostic criteria for triglyceride deposit cardiomyovasculopathy (TGCV). However, decreased BMIPP uptake in the early images, as in old myocardial infarction (OMI), would also cause a markedly decreased WR. Since the distinction between these clinical conditions cannot be made based on WR alone, simultaneous evaluation of the counts in the early image and WR is needed to properly understand the cardiac pathophysiology.

Purpose
To differentiate between TGCV and non-TGCV with OMI, both of which show decreased BMIPP WR, a new Count-WR Map (CWRM) method was evaluated. The purpose is to visually and easily distinguish between the two conditions using CWRM.

Methods
We introduced a CWRM consisting of two axes: counting in the early image, and WR. The count window was set to a maximum of the mean plus two standard deviations and a minimum of 50 counts, and the WR window was set to a maximum of 30 % and a minimum of -20%. CWRM was visually evaluated as normal, TGCV, non-TGCV with OMI, or TGCV with OMI.

Results
In normal cases, sufficient counts were observed in the early images, and WR did not decrease; CWRM showed light blue. In TGCV, sufficient counts were observed in the early image, but WRs markedly decreased; CWRM showed even orange. In non-TGCV with OMI, regions with decreased and preserved counts coexisted; CWRM showed light blue in the normal and black in the OMI region. In TGCV with OMI, CWRM showed orange in the TGCV myocardium and black in the OMI region (figure).

Conclusions
CWRM is useful for visually and easily differentiating TGCV from non-TGCV with OMI. CWRM can be applied to other cardiovascular diseases with count and WR variations for visual classification.
Lipoprotein(a) and cardiovascular prognosis of familial dyslipidemias: data from a 10-year follow-up study
Authors: Andrikou I , Skoumas I , Grigoriou K , Simantiris S , Dima I , Terentes D , Papanikolaou A , Kambaxis E , Tsioufis K , Vlachopoulos C 
Published: October 2024

Abstract

Background
Familial dyslipidemias, such as heterozygous familial hypercholesterolemia (FH) and familial combined hyperlipidemia (FCH) are associated with premature cardiovascular (CV) disease. On the other hand, increased lipoprotein(a) [Lp(a)] is considered as the most prevalent monogenic lipid disorder in the general population.

Purpose
This study aimed to longitudinally follow up two specific populations with familial dyslipidemias associated with increased CV risk, namely FH and FCH, and compare them with reference to their CV prognosis, investigating in parallel the effect of Lp(a) levels.

Methods
433 patients with FH (34% males, mean age 44.2±12.8 years) and 476 patients with FCH (57% males, mean age 49.0±11.1 years) from the outpatient lipid clinic of our hospital, without history of CV disease, who fulfilled the FH and FCH criteria, respectively, participated in the study. Participants were evaluated for a mean follow-up period of 9.6±7.6 years, with at least one annual visit. Venous blood samples were obtained at baseline in all patients for the determination of lipid profile and levels of Lp(a). All subjects were on lipid-lowering medication during the follow-up period. The endpoint of our study was the composite of major CV events (coronary artery disease events and stroke).

Results
The incidence of the composite endpoint of major CV events during the follow-up period in the total population was 6.5%, while it was greater in patients with FH compared to patients with FCH (8.1% vs 5.5%, p=0.03). Regarding CV risk factors, FCH compared to FH patients had greater prevalence of baseline hypertension (36% vs 9.7%, p&lt;0.001) and diabetes (11% vs 2%, p&lt;0.001), whereas FH patients had greater Lp(a) levels (37.4±40.3 vs 29.7±34.6 mg/dl, p&lt;0.01). Multiple Cox regression analysis revealed that FH patients had greater CV risk compared to FCH patients (HR 2.17, 95% CI 1.10-4.26, p=0.02). Moreover, in FH patients, increased baseline Lp(a) levels (≥30mg/dl) were an independent predictor of major adverse CV events (HR 2.37 95% CI 1.41-4.90, p=0.02), whereas in FCH patients increased Lp(a) was not an independent predictor. In FCH patients the presence of diabetes at baseline was a strong independent prognosticator of adverse CV events (HR 3.56 95% CI 1.19-11.33, p=0.03), after adjustment for confounding factors.

Conclusions
FH patients have greater CV risk compared to FCH patients. In FH patients, the presence of increased Lp(a) doubles the CV risk, beyond low density lipoprotein cholesterol levels. On the other hand, in FCH patients the presence of diabetes triples the CV risk, whereas Lp(a) does not convey an independent prognostic value.
The association between remnant cholesterol and all-cause mortality and cardiovascular mortality was modified by aged in American adults: a retrospective cohort study
Authors: Du D J , Chen W H , Zhao Y , Li Z Y , Huang R C 
Published: October 2024

Abstract

Background
Limited evidence exists regarding the association between remnant cholesterol (RC) and both all-cause and cardiovascular mortality. Also, the effect of age on the association between RC and the risk of mortality in general population has not been studied comprehensively. Therefore, the aim of this study is to investigate how age modifies the relationship between RC and the risk of all-cause and cardiovascular mortality.

Methods
A total of 21722 participants aged over 18 years were obtained from the National Health and Nutrition Examination Survey (1999–2018) , with follow-up mortality outcomes records linked to the National Death Index (NDI) until December 31, 2019 and divided into two groups (&lt;65 years old and ≥65 years old).Weighted multivariable cox proportional hazards models and weighted restricted cubic spline (RCS) were used to estimate the relationship of RC with the risk of all-cause mortality and cardiovascular mortality among American adults. The age interaction between RC and all-cause mortality and cardiovascular mortality was assessed. Restricted cubic spline (RCS) and sensitivity analysis were also used.

Results
During a median 110-month follow-up, a total of 3176 (10.77%) all-cause deaths and 1002 (3.22%) cardiovascular related deaths were recorded. A significant age interaction between RC and all-cause or cardiovascular mortality was found. After adjusting for multiple potential confounding factors, higher RC was associated with an increased risk of all-cause mortality[RC per unit increase Hazard Ratio (HR) 1.45, 95% Confidence Interval (CI) 1.16–1.81, p=0.001] and cardiovascular mortality (RC per unit increase HR 1.80, 95% CI 1.15–2.84, p=0.010) specifically in the younger age group but not in the older age group. Consistent findings were observed in restricted cubic spline analyses and sensitivity analyses.

Conclusion
In our study, we observed that the association between serum RC and all-cause mortality and cardiovascular mortality was modified by age. Specifically, higher RC levels were found to be significantly associated with an increased risk of all-cause mortality and cardiovascular mortality exclusively in patients below 65 years old. This novel finding warrants further confirmation through randomized controlled trials to provide robust evidence.
Clinical Deep Data Accumulation System (CLIDAS) reveals a "Lipid paradox" of hypertriglyceridemia in Japanese patients
Authors: Katsuki S , Kawahara T , Nakano Y , Kimura M , Rissei H , Matoba T 
Published: October 2024

Abstract

Background
The association between triglycerides (TG), HDL cholesterol (HDL-C) and the prognosis of cardiovascular disease has not been established.

Purpose
The aim of this study was to elucidate the relationships between the combination of TG and HDL-C levels and the risk of a major adverse cardiac and cerebral events (MACCE) and to verify the usefulness of TG and HDL-C as a risk stratification factor using the Clinical Deep Data Accumulation System (CLIDAS) database.

Methods
CLIDAS is a database that accumlates electronic medical records in seven tertiary hospitals in Japan including patient characteristics, medications, laboratory test, physiological test, cardiac catheterization, and PCI treatment. We analyzed 9,690 patients who underwent PCI between April 2014 and March 2020. These patients were stratified into the acute coronary syndrome (ACS) group (N=4,135; 43%) and the chronic coronary syndrome (CCS) group (N=5,555; 57%). Furthermore, patients were divided into four groups based on mean serum TG levels (175 mg/dL) and HDL-C levels (40 mg/dL) as cutoff values: high TG/low HDL-C, low TG/low HDL-C, high TG/high HDL-C, and low TG/high HDL-C, and compared for major adverse cardiac and cerebrovascular events (MACCE). The median follow-up duration was 2.5 years.

Results
The patients with high TG/low HDL-C showed the highest event rates in myocardial infarction among the ACS group. The hazard ratio for high TG/low HDL-C versus low TG/high HDL-C was 1.76 (95% CI, 1.08 to 2.87, P &lt; 0.05) after adjustment for age, sex, eGFR, and mean LDL-C levels, while we observed no risk stratification by the combination of TG and HDL-C levels in the CCS group (Figure 1). In contrast, the patients with low TG levels showed the paradoxically higher event rates of MACCE in both the ACS and CCS groups, as well as cardiovascular death in the CCS group, compared to those with high TG levels (Figure 2). The hazard ratio for low TG/low HDL-C versus high TG/low HDL-C was 3.21 (95% CI, 1.44 to 7.13, P &lt;0.005), and the hazard ratio for low TG/high HDL-C versus high TG/high HDL-C was 2.23 (95% CI, 1.03 to 4.84, P &lt; 0.05) in the CCS group after adjustment for age, sex, eGFR, and mean LDL-C levels.

Conclusion
In the CLIDAS database, while high TG and low HDL-C levels stratified the risk of ACS, low TG levels showed worsening prognosis for CV death, suggesting a "Lipid paradox" in the real world.Figure 1Figure 2