bluuebunny/crossref_metadata_2025_split huggingface dataset:
Proteomics associated with coronary high-risk plaque features on optical coherence tomography
Authors: Niida T , Yuki H , Suzuki K , Kinoshita D , Nakajima A , Mcnulty I , Lee H , Tanriverdi K , Shah R , Freedman J , Nakamura S , Jang I K 
Published: November 2023

Abstract

Introduction
Cardiovascular disease is the major cause of death worldwide. The physiological status of the cardiovascular system is reflected in plasma proteins and a newly developed technique based on proximity extension assays has enabled the analysis of a broad range of protein biomarkers associated with cardiovascular disease. However, biomarkers for coronary high-risk plaques, including lipid-rich plaques, macrophages, cholesterol crystals, and microvessels, have not yet been found.

Purpose
This study aimed to identify proteins specific for coronary high-risk plaques.

Methods
We analyzed 57 patients (71.1 ± 10.6 years, male: 68.4%) who underwent intracoronary optical coherence tomography and provided blood samples for proteomic analysis. Forty-seven patients (86.0%) had lipid-rich plaques, 46 patients (80.7%) had macrophages, 16 patients (28.1%) had cholesterol crystals, and 27 patients (47.4%) had microvessels. A total of 1,470 plasma proteins were analyzed using the Olink® Explore 1,536 Reagent Kit and P2 100 cycle reagent kit on a NextSeq 2000 sequencer.

Results
In patients with lipid-rich plaques, the protein expressions of Interstitial collagenase (MMP1), Wiskott-Aldrich syndrome protein family member 1 (WASF1), and Protein phosphatase 1 regulatory subunit 12A (PPP1R12RA) were significantly increased, while the expressions of Fc receptor-like protein 3 (FCRL3), Folate receptor gamma (FOLR3), Cobalamin binding intrinsic factor (CBLIF), Glutathione S-transferase A1 (GSTA1), and Keratin, type I cytoskeletal 18 (KRT18) were significantly decreased (Figure A). In patients with macrophages, the protein expressions of MMP1, WASF1, PPP1R12RA, and Scavenger receptor cysteine-rich domain-containing group B protein (SSC4D) were significantly increased, while the expressions of Fatty acid-binding protein, intestinal (FABP2), FOLR3, CBLIF, GSTA1, and Fibroblast growth factor 21 (FGF21) were significantly decreased (Figure B). In patients with cholesterol crystals, the protein expressions of FOLR3, Secreted frizzled-related protein 1 (SFRP1), and Anterior gradient protein 2 homolog (AGR2) were significantly decreased (Figure C). In patients with microvessels, the expression of FOLR3 was significantly decreased (Figure D).

Conclusion
These proteins might be new biomarkers in patients with coronary high-risk plaques.
Low-density lipoprotein cholesterol reduction and short-term incidence of ASCVD in the population-based cohort study LATINO
Authors: Seabra Carvalho D , Gavina C , Afonso-Silva M , Canelas-Pais M , Araujo F 
Published: November 2023

Abstract

Background/Introduction
In Portugal, 25,000 people die from atherosclerotic cardiovascular diseases (ASCVD) every year, accounting for more than 20% of all deaths in 2019. Reducing low-density lipoprotein cholesterol (LDL-C) is an effective intervention to lower the risk of CV events, including ischemic stroke (IS), coronary heart disease (CHD) and Peripheral Artery Disease (PAD).

Purpose
This study aims to assess the extent of ASCVD risk prevention associated with different levels of LDL-C lowering in an unselected population in Portugal.

Methods
We used electronic health records to conduct a population-level retrospective cohort study of individuals aged 40–80 years who were followed in 1 hospital and 14 primary care facilities in Portugal from 1/1/2012 to 31/12/2020. Patients started being followed when they fulfilled criteria to be exclusively characterised as high CV risk at the index date (defined according to the ESC/EAS 2019 guidelines).
This analysis focused on the 24-month risk of developing ASCVD, by percentual LDL-C reduction between 360 and 540 days from the maximum LDL-C. The primary endpoint of ASCVD included the risk of IS, CHD or PAD, as defined by the corresponding ICD-9-CM/ICD-10-CM codes. IS, CHD and PAD were also analysed separately as secondary endpoints. LDL-C values were obtained from laboratory results and CV and diabetes medications’ use from prescription data registered according to the Anatomical Therapeutic Chemical Classification System recorded. A Cox regression model adjusted for sex, age, all relevant CV risk variables, risk-enhancing factors, and CV and diabetes medications was developed.

Results
The total cohort at 24 months of follow-up consisted of 21,101 observations corresponding to 16,055 distinct patients. Higher LDL-C percentual reduction was associated with a lower risk of ASCVD, with adjusted hazard ratios (aHR) (95% confidence intervals (CI)) of 0.82 (0.66-1.02), 0.86 (0.66-1.11) and 0.44 (0.24-0.79) per reduction of ]0,30%], ]30,50%] and ]50,90%] of LDL-C respectively, versus having no reduction or increase. IS was the secondary endpoint that contributed the most to the reduction of risk of ASCVD with an aHR (95% CI) of 0.89 (0.69-1.15), 0.67 (0.47-0.96) and 0.41 (0.19-0.86) for the same corresponding LDL-C reduction categories. However, these results were not statistically significant for PAD or CHD when assessed isolated.

Conclusion
This real-world evidence study shows that, independently of age, sex, and other CV risks and medications, reductions of &gt;50% in LDL-C significantly reduced by 56% the risk of ASCVD at 24 months in high CV risk patients. This reduction was more striking for ischemic stroke. Therefore, LDL-C reductions &gt;50% should be a paramount objective in public health policies worldwide.
Course of the effects of LDL-cholesterol reduction on cardiovascular risk over time: a meta-analysis of 59 trials
Authors: Burger P M , Dorresteijn J A N , Koudstaal S , Mosterd A , Visseren F L J 
Published: November 2023

Abstract

Background
Therapies lowering low-density lipoprotein cholesterol (LDL-c) are widely used to reduce cardiovascular disease (CVD) risk in patients with or at high risk of CVD. Therapy is usually continued lifelong, but whether the effects of LDL-c reduction remain stable over time is uncertain. This study aimed to establish the course of the relative treatment effects of LDL-c reduction on cardiovascular risk over time, i.e. treatment duration and age.

Methods
Randomized controlled trials (RCTs) of LDL-c lowering therapies were identified through a search in MEDLINE and EMBASE (1966-January 2023). RCTs of guideline-recommended therapies (i.e. statins, ezetimibe, and proprotein convertase subtilisin–kexin type 9 inhibitors [PCSK9i]) were selected for the primary analyses, with RCTs of other therapies included in sensitivity analyses. Random-effects meta-analyses were performed to establish the average relative risk (RR) for major vascular events (cardiovascular death, myocardial infarction or other acute coronary syndrome, coronary revascularization, or stroke) per 1 mmol/L LDL-c reduction. Course of the effects over time was assessed using random-effects meta-regression analyses for the association between follow-up duration, age, and the RR for major vascular events per 1 mmol/L LDL-c reduction. Analyses were also stratified for primary and secondary prevention.

Results
A total of 59 trials (26 statin trials, 2 ezetimibe trials, 3 statin/ezetimibe combination trials, 7 PCSK9i trials, and 21 other trials) were selected, including 394,989 participants and 49,642 major vascular events. Mean follow-up was 3.9 years (range 0.9-9.7), and age was 63.8 years (range 48.0-77.0). The average RR for major vascular events per 1 mmol/L LDL-c reduction was 0.78 (95% confidence interval [CI] 0.75-0.81), with slightly larger risk reductions in primary (RR 0.74; 95% CI 0.68-0.81) as compared to secondary prevention (RR 0.80; 95% CI 0.77-0.83). Follow-up duration was not associated with the RR for major vascular events (p = 0.615), with the meta-regression line showing a stable RR over follow-up time (RR for change per year 0.994; 95% CI 0.971-1.017). The RR for major vascular events increased (i.e. risk reduction decreased) with age in primary prevention (RR for change per 5 years 1.094; 95% CI 1.028-1.165; p = 0.018), but remained largely unchanged in secondary prevention (RR for change per 5 years 0.986; 95% CI 0.943-1.031; p = 0.533). Consistent results were found for statin trials only, and all trials combined.

Conclusions
The relative treatment effects of LDL-c reduction are stable over time in secondary prevention, but may decrease with age in primary prevention.Meta-analysisMeta-regression analyses
Effects of icosapent ethyl on residual cardiovascular risk according to predicted baseline risk: results from REDUCE-IT
Authors: Burger P M , Bhatt D L , Dorresteijn J A N , Steg P G , Koudstaal S , Mosterd A , Martens F M A C , Visseren F L J 
Published: November 2023

Abstract

Background
Icosapent ethyl is recommended by the ESC CVD Prevention Guidelines as one of the intensified prevention strategies to be considered in patients with established CVD and a high residual risk.[1] Treatment effects of icosapent ethyl may vary between individual patients. This study aimed to determine the relative and absolute treatment effects of icosapent ethyl according to baseline CVD risk.

Methods
Participants from the REDUCE-IT trial with established CVD were included (n = 5,785).[2] Baseline 5-year risk of major adverse cardiovascular events (MACE), defined here as cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke was estimated using the ESC guideline-recommended SMART2 risk score.[3] Modification of the relative treatment effect of icosapent ethyl by baseline risk was assessed using a Cox proportional hazards model including a treatment-by-risk interaction. Next, relative treatment effects were derived stratified by quartiles of baseline risk. The observed 5-year absolute risk reduction (ARR) with icosapent ethyl within each risk quartile was assessed based on Kaplan-Meier estimates of the cumulative incidence of MACE.

Results
During a median follow-up of 4.8 years (interquartile range 3.2-5.3), 361 MACE events occurred in the icosapent ethyl group vs 489 in the placebo group (hazard ratio [HR] 0.72; 95% confidence interval [CI] 0.63-0.82). Mean predicted vs observed 5-year risk of MACE was 9.1% vs 10.2% in the first quartile (range 3.6-11.4%), 13.8% vs 14.6% in the second quartile (range 11.5-16.0%), 19.2% vs 19.5% in the third quartile (range 16.1-23.4%), and 33.4% vs 32.2% in the fourth quartile (range 23.5-83.0%). Icosapent ethyl significantly reduced MACE in all risk quartiles, with an HR (95% CI) of 0.62 (0.43-0.88), 0.66 (0.48-0.92), 0.69 (0.53-0.90), and 0.78 (0.63-0.96) respectively (p for treatment-by-risk interaction = 0.06). The 5-year ARR (95% CI) with icosapent ethyl increased across risk quartiles, i.e. was 5.3% (1.8-8.7%), 5.6% (1.9-9.4%), 7.4% (3.0-11.8%), and 10.8% (5.3-16.2%) respectively (Figure). This translates to a number needed to treat (NNT; 95% CI) of 19 (11-54), 18 (11-52), 14 (8-34), and 9 (6-19).

Conclusions
Among CVD patients with elevated triglyceride levels, icosapent ethyl significantly reduces the risk of MACE in individuals with a low, moderate, and high baseline risk. Absolute treatment benefits are largest for patients at the highest risk, as reflected by the twofold increase in ARR and decrease in NNT in the highest as compared to the lowest risk quartile.Icosapent ethyl effect in risk quartiles
Effect of smoking initiation age on nicotine dependence
Authors: Komiyama M , Swati M , Yamakage H , Morimoto T , Hasegawa K 
Published: November 2023

Abstract

Background
Tobacco is widely recognized as a risk factor for major cardiovascular morbidity and mortality worldwide. Although the legal smoking age to purchase tobacco is 18 years old (yo) in most countries in the world but it ranges from 15 to 21 yo. If a person does not start using tobacco until the age of 21, they are more likely to remain tobacco-free for the rest of their lives. In 2019, the Tobacco 21 [T21] federal law came into effect in 2019 in the US, where the US government raised the minimum age for purchasing tobacco products from 18 to 21 yo and saw a subsequent decline in tobacco use. People who start smoking at a young age show greater nicotine dependence, and lower quit rates. However, the details of the effect of smoking initiation age on the smoking cessation (SC) rates and nicotine dependence are not known.

Purpose
The purpose of this study is to demonstrate the effect of age at smoking initiation on SC rate, and nicotine dependence using 20 yo as the cut-off point, which is the legal smoking age in Japan. We also examined the effect of age at smoking initiation on various smoking related parameters.

Methods
Among smokers who visited our SC clinics, the participants (smokers) who visited our SC clinics were divided into 2 groups (&lt;20 yo and ≥20 yo) and 4 groups (≤17 yo, 18-19 yo, 20-21 yo, ≥22 yo) based on their age of smoking initiation. The prevalence and association between the various parameters including CV biomarkers were compared between 2 groups by using Fisher’s exact test, and unpaired t-test.

Results
The study participants consisted of 1382 smokers [29.8% female] with a mean age of 58.2±13.1 yo at the time of first visit to our clinic. Compared with the group of smoking initiation age of ≥20 yo, the group of smoking initiation age group &lt;20 yo reported a higher number of cigarettes/day (25±12 vs 22±12, p value&lt;0.001 and adjusted p-value=0.002), higher respiratory CO levels (19.3±13.5 vs16.5±11.9), and higher FTND score (7.4±2.0 vs 6.3±2.2) with significant p-values and adjusted p-value of &lt;0.001. The successful SC rate was lower in the group ≥20 yo with 56% as compared to the group &lt;20 yo with 45.5% (p-value=0.001). When comparing the 4 groups, a further increase in the age of smoking initiation to ≥22 yo leads to an additional decrease in nicotine dependence.

Conclusions
The present study shows that smoking initiation at the age of 20 yo or older is associated with lower nicotine dependence and depressive tendency, and a higher rate of successful SC compared with smoking initiation at age &lt;20 yo. A further increase in the age of smoking initiation age to 22 yo or older leads to a further decrease in nicotine dependence. Our study may explain the rationale for reducing smoking through the T21 policy in the USA. The present study underlines the importance of raising the legal age of tobacco purchase to 22 yo worldwide.
Increased inflammatory proteins in patients with severe obesity is associated with persistent myocardial dysfunction one year after bariatric surgery. The FatWest study
Authors: Grymyr L M , Mellgren G , Meyer K , Gerdts E , Nadirpour S , Ferno J , Nedrebo B , Cramariuc D 
Published: November 2023

Abstract

Background
Over half of patients with severe obesity have subclinical cardiac dysfunction and about 40% maintain impaired left ventricular (LV) mechanics one year after bariatric surgery despite impressive weight reduction.

Purpose
To investigate whether measurement of serum markers of chronic inflammation before bariatric surgery can help identify patients with persistent postoperative cardiac dysfunction.

Methods
In the prospective FatWest (Bariatric Surgery on the West Coast of Norway) study 75 patients with severe obesity (44±9 years, 72% women, body mass index [BMI] 41.5±4.7 kg/m², 56% with hypertension) underwent echocardiography before and 1 year after Roux-en-Y gastric bypass surgery. We assessed LV mechanics in the radial and longitudinal direction by the midwall shortening (MWS) and global longitudinal strain (GLS). Myocardial oxygen (O2) demand was derived from the LV mass-wall stress-heart rate product. Inflammation was assessed by high-sensitive C-reactive protein, serum amyloid A and calprotectin in biobank samples.

Results
Preoperatively, patients with low MWS (45% of the group) had increased high-sensitive C-reactive protein, total calprotectin, and several amyloid A isoforms, and patients with high myocardial O2 demand (20%) had high total calprotectin (all p&lt;0.05). In the whole study population, bariatric surgery induced a significant improvement in both BMI (12.6±3.7 kg/m²), GLS (4.74±5.20%), myocardial O2 demand and inflammatory proteins (Figure A, all p&lt;0.001). However, there were no significant improvement in MWS, and 33% of patients still had low MWS at the 1-year control.
In logistic regression analyses, after adjustment for sex, BMI and hypertension, increased preoperative serum total calprotectin was independently associated with high myocardial O2 demand both pre- and postoperatively (Nagelkerke R² 0.47 and 0.51, p&lt;0.05). In similar analyses, higher preoperative serum total amyloid A was related to low MWS and high myocardial O2 demand 1 year after surgery (Nagelkerke R² 0.55 and 0.51, p&lt;0.05). A simple preoperative risk score based on sex, hypertension, biplane ejection fraction, and serum total amyloid A above 4.0 mg/ml predicted low 1-year MWS with 79% sensitivity and 75% specificity at a value of 1.75 in Receiver Operating Characteristic (ROC) analysis (AUC 0.80, p&lt;0.001) (Figure B). Low GLS was not predicted by inflammatory biomarkers at any timepoint.

Conclusion
Increased serum concentration of inflammatory proteins in patients with severe obesity is linked to persistently elevated myocardial O2 demand and impaired LV midwall mechanics 1 year after bariatric surgery.Figure AFigure B
Association between body mass index and outcomes in heart failure across the ejection fraction spectrum: data from the Swedish Heart Failure Registry
Authors: Ferrannini G , Rodolico D , Amario D D , Dahlstrom U , Lund L H , Savarese G 
Published: November 2023

Abstract

Background
Despite overweight/obesity being a well-known cardiovascular (CV) risk factor, high body mass index (BMI) has been suggested to be associated with longer survival in patients with heart failure (HF). Data on large populations are lacking, as well as whether this advantage might be consistent across the ejection fraction (EF) spectrum, i.e. reduced (HFrEF), mildly reduced (HFmrEF) and preserved (HFpEF, where obesity may have a greater causative role).

Purpose
To assess the association between BMI and outcomes in a large and unselected contemporary cohort of patients with HF across the EF spectrum.

Methods
Patients with HF registered in the Swedish HF Registry (SwedeHF) between May 2000 and December 2021, with no missing values for EF and BMI, were selected. Linkage with the Cause of Death Registry and the National Patient Registry provided data on mortality, hospitalizations and comorbidities. Patients were categorised according to BMI class (underweight &lt;18.5 kg/m2; normal weight 18.5-24.9 kg/m2; overweight 25.0-29.9 kg/m2; obesity&gt;30-34.9 kg/m2).
The primary outcome was all-cause death, secondary outcomes were CV death and HF hospitalization (HHF). The associations between BMI categories and outcomes were analysed by univariable and multivariable Cox proportional hazards models, both in the whole cohort and according to EF classes; this association was also explored by modeling BMI as a continuous variable through restricted cubic splines. Missing data were handled by chained equation multiple imputation.

Results
69,874 patients (mean age 74 years, 36% females) were included, of whom 3% underweight, 35% with normal weight, 35 % overweight, obese 27%. Figure 1 reports the proportions of the different BMI categories according to EF: obesity was significantly more common in HFpEF. Regardless of EF, obese patients were younger, with lower N-terminal B-type natriuretic peptide, higher New York Heart Association class, and with diabetes and hypertension as compared with the other three BMI classes.
Compared with normal weight, both overweight and obesity were independently associated with lower mortality risk, while underweight with higher mortality, with consistent results in HFrEF, HFmrEF and HFpEF; the same associations were found for CV death or all three EF classes, while underweight only was associated with HHF in HFrEF. When BMI was modelled as restricted cubic splines, a reverse J-shaped adjusted association was found between BMI and risk of all-cause death (Figure 2).

Conclusion
HF patients with overweight and obesity had a lower mortality risk compared with patients with normal or underweight patients across all EF classes, at least up to BMI&gt;40 kg/m2. Our results are consistent with the previously suggested potential survival benefit in overweight patients, calling for future research to understand this apparent paradox.Figure 1
Five-year changes in weight and risk of atrial fibrillation in women and men from the Danish diet, cancer, and health cohort
Authors: Frederiksen T C , Christiansen M C , Benjamin E J , Overvad K , Olsen A , Dahm C C , Jensen H K 
Published: November 2023

Abstract

Background
Overweight and obesity are causal risk factors for atrial fibrillation (AF).(1) Mendelian randomization studies indicated a higher risk of AF with each unit increase in body mass index (BMI).(1) In observational studies, weight gain was associated with a higher risk of incident AF compared to stable weight.(2,3) However, the results are conflicting regarding the association between weight loss and risk of incident AF.(4,5).

Purpose
We aimed to assess the association between five-year changes in weight and absolute and relative rates of incident AF in women and men from the Danish Diet, Cancer, and Health Cohort.

Methods
In the Danish cohort study Diet, Cancer, and Health, participants were invited to attend a recruitment research examination and a second examination 5 years later. Height, weight, and several lifestyle factors were assessed at both examinations. We calculated BMI and BMI changes between first and second examination. BMI changes were categorized into following groups: &lt;-5 kg/m2, ≥-5 to &lt;-2.5 kg/m2, ≥-2.5 to &lt;2.5 kg/m2, ≥2.5 to &lt;5 kg/m2 and ≥5 kg/m2. Diagnoses of AF and comorbidities were retrieved from the Danish National Patient Registry. We used multivariable-adjusted Cox proportional hazards models to assess hazard ratios (HR) of AF according to changes in BMI.

Results
43,758 participants without prior AF were included in the study. The median age was 62 (25th-75th percentile, 58-66) years and 54% were women. Over 15.7 years median follow-up time 5,312 participants had incident AF. From the first to the second measure, 39,076 (89%) of participants had stable weight, 2,627 (6%) lost weight, and 2,055 (5%) gained weight. The incidence rates of AF per 1,000 person-years were 8.4 (95% CI 8.1-8.6) among participants with stable weight, 12.4 (95% CI 9.6-16.1) among those with weight loss ≥5 kg/m2, and 15.4 (95% CI 11.7-20.2) among those who gained ≥5 kg/m2. Compared to participants with stable weight, individuals who gained ≥2.5 to &lt;5 kg/m2 had a higher hazard of AF (HR 1.24, 95% CI 1.09-1.41). Among participants who gained ≥5 kg/m2 the rate of AF was also higher compared to stable weight (HR 1.95, 95% CI 1.48-2.56). There was no statistically significant association between weight loss, regardless of degree, and rate of AF. Figure 1 shows the HR of AF by BMI changes from first to second measure compared to stable weight using restricted cubic splines. In sex-stratified analyses, the association between weight gain of ≥5 BMI units (kg/m2) and higher AF rate was present for both women and men.

Conclusions
In this cohort study, five-year weight gain was associated with higher long-term risk of AF compared to stable weight. However, we found no associations between weight loss and long-term risk of AF.Figure 1