bluuebunny/crossref_metadata_2025_split huggingface dataset:
Common carotid artery inima-media thickness trajectories over time are more strongly associated with incident cardiovascular disease than a one off measurement
Authors: Pavey H , Tschiderer L M , Seekircher L , Willeit P 
Published: June 2024

Abstract

Background
Atherosclerotic cardiovascular disease (CVD) remains the leading cause of mortality and morbidity globally. Several studies have previously looked into whether carotid artery intima-media thickness (CCA-IMT) measured at a single point in time is associated with CVD risk. More recent analyses have considered progression of CCA-IMT over time as a risk predictor, but measurement of progression is particularly prone to measurement error. Modelling the trajectories allows estimating the true strength of the aetiological association with CVD risk more accurately.

Purpose
The aim of the present study is (i) to model within-person trajectories of CCA-IMT incorporating repeat measurements taken over an extended period of time, thereby reducing measurement error, and (ii) to quantify the association of within-person CCA-IMT trajectories over time with the risk of a CVD event.

Methods
Individual participant data from studies within the Proof-ATHERO consortium were used for this analysis. The Proof-ATHERO consortium collates data from studies with information on atherosclerosis measures, CV risk factors and CV outcomes. Study-specific joint longitudinal and survival models were fitted to model the association between CCA-IMT trajectory and CVD risk, accounting for conventional CV risk factors including: age, sex, systolic blood pressure (SBP), high-density lipoprotein cholesterol (HDL-C), total cholesterol, smoking status, history of diabetes and history of CVD. Study-specific hazard ratios were pooled in a random effects meta-analysis.

Results
Data from 38 studies were analysed, involving 68,077 individuals and 153,643 CCA-IMT measurements. 51% of the individuals were female, the weighted mean (SD) age of participants at baseline was 61 (9) years, 13% of individuals had a history of CVD. Over a median (5th percentile, 95th percentile) follow-up of 7.3 (0, 28.6) years, 13,116 (19.3%) individuals suffered an incident CVD event. At baseline, the weighted mean (SD) CCA-IMT was 0.83 (0.19) mm, SBP was 135 (19) mmHg, HDL-C was 1.29 (0.40) mmol/L, total cholesterol was 5.49 (1.06) mmol/L; 26% were current smokers and 16% had a history of diabetes. Trajectories of CCA-IMT were independently associated with CVD risk after accounting for conventional CVD risk factors. The pooled adjusted hazard ratio for CVD (95% CI) per study-specific SD higher CCA-IMT value was 1.20 (1.14-1.27) (p&lt;0.001). In comparison, a one off measurement of CCA-IMT at baseline was associated with a pooled hazard ratio of 1.11 (1.06-1.16) per study-specific SD higher value (p&lt;0.001).

Conclusion
The association of CCA-IMT trajectories based on repeated measurements with incident CVD risk is stronger than the association of a one off measurement.
Distribution of cardiovascular disease risk in adults aged 40 to 79 years with diagnosed hypertension but not on medications: findings from nationwide cross-sectional studies
Authors: Wang S , Yang Z 
Published: June 2024

Abstract

Background
Hypertension is the most important modifiable risk factor for cardiovascular disease (CVD). Many people with diagnosed hypertension are not receiving drug treatment, partly because they perceive their CVD risk as low. However, the distribution of CVD risk among these people remained largely unknown.

Purpose
To depict the risk of future CVD event, either first or recurrent, among people with diagnosed hypertension but not on antihypertensive drug treatment.

Methods
Participants aged 40-79 years who reported doctor-diagnosed hypertension but not on medications were identified from National Health and Nutrition Examination Surveys 1999 to 2018. Among them, the participants with known CVD, and those without known CVD but had complete data for estimating their 10-year predicted CVD risk, were included in the study. The 10-year predicted CVD risk was calculated using Pooled Cohort Equations as recommended in the 2019 American College of Cardiology/American Heart Association guideline on the primary prevention of CVD. The participants were categorised into 1) high risk if having known CVD, or a 10-year predicted CVD risk ≥10%; 2) low risk if having a 10-year predicted CVD risk &lt;10%. The proportion of each risk group was calculated with the mobile examination center sample weights incorporated to account for the potential oversampling and non-response. The differences between subgroups in the distribution of CVD risk were assessed using Chi-squared test.

Results
Of the 2563 participants included, 1119 had known major CVD (n=396, 15.45%) or a 10-year predicted CVD risk ≥10% (n=723, 28.21%), corresponding to a weighted proportion of 35.75% (95% confidence interval: 32.99 to 38.50%), while the other participants had a low 10-year predicted CVD risk (weighted proportion: 64.25%, 61.50 to 67.01%). The proportions of high-risk participants were much higher in the elderly (71.63% for 60-79 years) and males (45.37%) than in others (both P&lt;0.001). These patterns were consistent across ten survey cycles from 1999 to 2018.

Conclusions
One third of the US adults aged 40-79 years with diagnosed hypertension but not on medications had known CVD or a 10-year predicted CVD risk ≥10%, corresponding to over 3 million individuals. This proportion was little changed over the past two decades, highlighting the need for improvement in the management of CVD and its risk factors.
Menopause increases the risk of diabetes, and this association might be due to iron metabolism
Authors: Ahanchi N , Kutalik Z , Marques-Vidal P 
Published: June 2024

Abstract

Introduction
Type 2 diabetes mellitus (T2DM) is a serious public health concern with a considerable impact on human life and health expenditures. Interestingly, Emerging evidence indicates that the risk and clinical features of cardiometabolic diseases, like T2DM, may vary among women based on their menopausal status (Figure1). In addition to hormonal changes, iron and its markers have been closely related to glucose metabolism and T2DM. Increased serum ferritin, reflecting body iron overload, is often associated with elevated blood glucose and insulin levels, as well as with increased risk of insulin resistance. One the other hand, iron biomarker levels differ in females in different reproductive stages.

Goals
In this study, we aimed to investigate: 1) the association of menopausal status with T2DM risk, and 2) the association of menopause with iron biomarkers and of iron biomarkers with T2DM risk.

Method
Data from the prospective CoLaus|PsyCoLaus study, conducted in our city. Of the initial 3544 women aged 35-75, 2002 (55.8% of the initial sample) were eligible for analysis after applying exclusion criteria. The associations between menopause and incidence of T2DM were assessed using time-varying Cox models, and linear mixed models assessed how changes in menopause status influenced iron biomarkers during this period. Subsequently, a time-varying Cox model investigated the association between iron biomarkers and incident T2DM.

Result
After adjustment for potential confounders (age , BMI , smoking status , hormone replacement therapy use, C-Reactive Protein), menopause status was associated with an increased risk of T2DM: multivariable-adjusted hazard ratio (HR) 2.88 (95% CI: 1.91-3.81). Non-significant associations with risk of T2DM were observed for iron (HR: 1.06, 95% CI: 0.59-2.98), ferritin (HR: 1.09, 95% CI: 0.85-1.38), or TSAT (HR: 0.98, 95% CI: 0.88-1.05), while transferrin demonstrated a significant positive association (HR: 1.33, 95% CI: 1.11-1.58). In a multivariable-adjusted linear mixed model investigating the longitudinal relationship between menopause status and iron biomarkers, a statistically significant association was found for all evaluated iron biomarkers (Table1).

Conclusion
We found a significant association between menopause status and risk of T2DM, and between transferrin and risk of T2DM. Changes in transferrin levels could partly explain the increased risk of T2DM observed after menopause.
Associations of anthropometric markers with arterio-venous ratio in the general population
Authors: Davoodzadeh S , Ittermann T , Schipf S , Volzke H , Bahls M , Soori R , Doerr M , Ricardo Paulista Markus M 
Published: June 2024

Abstract

Background
Overweight and obesity are major contributors to the worldwide burden of cardiovascular diseases. Structural changes within the human retinal vasculature may reflect early cardiovascular aging.

Purpose
The aim of our analyses was to investigate the associations of traditional anthropometry markers, body composition and fat distribution with parameters of retinal fundoscopy in a population-based study.

Methods
We performed cross-sectional analyses of 3,162 participants (1,659 women, 52.5%) aged 20 to 82 years from the baseline examination of the second independent population-based cohort of the Study of Health in Pomerania (SHIP-TREND-0) realized between 2008 and 2012. The associations of anthropometric parameters (body height and weight, body mass index [BMI], waist circumference [WC], hip circumference [HC], waist-to-hip ratio [WHR], waist-to-height ratio [WHtR]), body composition (fat mass [FM] and relative fat-free mass [RFFM] assessed by bioelectrical impedance analysis), and fat distribution markers (subcutaneous adipose tissue [SAT], and visceral adipose tissue [VAT] from magnetic resonance imaging) with the arterio-venous ratio (AVR) were analyzed by multivariable linear and logistic regression models adjusted for age, sex and smoking status. All exposure variables were standardized in the regression models. The AVR was calculated from the measurements of the central retinal artery equivalent (CRAE) and the central retinal vein equivalent (CRVE), which reflect the estimated diameter of the central retinal artery and vein. CRAE and CRVE were measured by fundus photography and static vessel analysis of the central retina. Moreover, an AVR &lt; 0.8 was defined as decreased AVR.

Results
While RFFM was positively associated with the AVR (ß=1.11; 95% confidence interval [CI]: 0.81 to 1.41; p&lt;0.001), all the other markers were inversely associated with AVR. Specifically, VAT showed the strongest inverse association with AVR (ß= -1.07; 95% CI: -1.49 to -0.65; p&lt;0.001). In line with these results, RFFM was associated with a 0.76 (95%CI: 0.68 to 0.86; p&lt;0.001) lower chance for a prevalent decreased AVR, while VAT was associated with a higher chance for a prevalent decreased AVR (odds ratio [OR]=1.40, 95%CI: 1.20 to 1.63; p&lt;0.001) (Table 1).

Conclusions
Our results substantiate evidence of a deleterious inverse association between body markers derived from fat content, composition and distribution with the arterio-venous ratio. Importantly, and oppositely to that, we found a beneficial positive association of fat-free mass with the arterio-venous ratio. Our findings suggest a health effect of fat-free mass and a detrimental influence of fat mass on the circulatory system.
Cholesterol paradox for cardiac events: is age the missing link?
Authors: Meng J , Bhalraam U , Merinopoulos I , Eccleshall S , Tsampasian V , Vassiliou V 
Published: June 2024

Abstract

Background
Hypercholesterolemia is a recognized risk factor for cardiovascular disease; however, the ‘cholesterol paradox’, where lower cholesterol levels are associated with worse outcomes, challenges traditional understanding. The aetiology of this paradox remains unclear.

Purpose
To explore the cholesterol paradox, our study aims to determine if reverse causality and age-related factors contribute to this phenomenon. We hypothesise that in older adults, lower cholesterol levels may be indicative of poorer baseline health and nutritional status. Consequently, this could lead to higher mortality following percutaneous coronary intervention (PCI).

Methods
In a retrospective analysis of 1237 patients (median age 69; IQR [61 - 75]) undergoing PCI for stable angina from January 2015 to November 2019, we categorised patients based on presence or absence of hypercholesterolemia history. We employed cumulative hazard plots to compare all-cause mortality (ACM) and cardiovascular mortality (CVM) and conducted correlation tests between age and cholesterol levels.

Results
Consistent with the cholesterol paradox, a significant reduction in ACM was observed in patients with hypercholesterolemia history (HR 0.44, 95%CI(0.26 – 0.74), p = 0.0014). Intriguingly, CVM did not show any significant difference between groups (HR 0.63, 95%CI(0.30 – 1.33), p = 0.23) [Figure 1]. An inverse correlation between age and hypercholesterolemia history was noted (Pearson Coeff: -0.14, p&lt;0.001).

Conclusion
The disparity in ACM, not paralleled by CVM, suggests non-cardiovascular factors may drive mortality in patients with lower cholesterol post-PCI. The inverse relationship between cholesterol levels and age supports the theory that cholesterol is influenced by the overall health status, and cholesterol acts as a surrogate biomarker for nutritional status and physiological reserve. These findings underscore the necessity for a multidisciplinary approach in managing patients with cardiovascular disease, where nutritional support and strategies to bolster physiological reserve, including physical activity, could play a critical role in improving outcomes.
The elucidation of the underlying mechanisms of the cholesterol paradox warrants further investigation. Prospective studies are needed to explore the causal relationships and to confirm if interventions aimed at improving overall health and nutritional status can positively impact outcomes in this population.
Our study sets the stage for such inquiries, highlighting the intricate interplay between lipid levels, age and mortality that extends beyond traditional cardiovascular risk factors.
Electrocardiographic manifestations in female team handball players
Authors: Malmgren A , Tragardh E , Gudmundsson P , Kjellstrom B , Stagmo M , Dencker M 
Published: June 2024

Abstract

Background
Long-term intensive training leads to structural, functional, and electrical remodeling of the heart. The effect of elite sports on the heart has not been fully investigated, particularly for female athletes.

Purpose
To investigate if electrocardiogram (ECG) morphology in elite female handball players show any changes of electrical remodeling compared to ECG in non-athlete female subjects, and if potential changes in ECG could be explained by changes in cardiac dimensions obtained by echocardiographic and exercised hours.

Methods
A cross-sectional study where elite female team handball players (athletes) were compared to sex and age-matched, non-athletic controls. All participants underwent a resting 12-lead ECG, an echocardiographic examination and answered a questionnaire about physical activity. Heart rate (HR), P-wave duration and P-wave amplitude, PQ duration, QRS duration, QT and QTc durations according to Bazett’s and Fridericia formulas were measured by the ECG system. Three different ECG criteria for left ventricular hypertrophy (LVH) were used. The sum of QRS voltage was measured in each of the 12-leads from the peak of the R wave to the nadir of either the Q wave or the S wave, whichever was deeper. Cornell and Sokolow & Lyon were also measured. A voltage-duration product for each LVH criterion was calculated by multiplying the voltage criterion by QRS duration. Echocardiographic measurement of left atrium diameter (LAd), left atrial volume (LAV), left ventricular internal diameter in diastole (LVIDd), left ventricular end-diastolic volume (LVEDV) and left ventricular mass (LVM) were performed using both 2-dimensional and 3-dimensional echocardiography and adjusted for body surface area (BSA). All echocardiographic and ECG variables were compared between the two groups using the Student’s t test and further on adjusted for cardiac dimensions using analysis of covariance (ANCOVA) test.

Results
The study included 33 female athletes and 33 controls, mean age 20±2 vs. 23±2 years. Athletes trained 10.8±2.3 hours per week compared to controls who performed less than 2 hours per week. The athletes had larger cardiac dimensions and lower heart rate and QTc duration compared to controls, see table I and II. Athletes had higher QRS and QT durations, 12-lead sum of voltage and 12-lead sum of voltage x QRS than controls, see table II. Changes in P-wave amplitude and duration could not be explained by left atrial dimensions and changes in 12-lead sum of voltage, QRS and QT could only in part be explained by left ventricular size, see table III.

Conclusions
Female handball players had altered ECGs and enlarged ventricular dimensions compared to controls. However, the changes in ECG could only be partly explained by the differences in left ventricular dimensions. This suggest that electrical changes caused by structural remodeling occur in the female handball players’ heart.
Association between apelin-12 and N-terminal pro-brain natriuretic peptide depending no- reflow phenomenon in STEMI patients
Authors: Krasniqi X , Kocinaj D , Vincelj J , Krasniqi F , Sejdiu B , Bakalli A 
Published: June 2024

Abstract

Background
In acute myocardial infarction, hypoxia, through the hypoxia inducible factor pathway, increases the level of apelin, protecting the myocardium from ischemia-reperfusion injury. In the absence of apelin, Ca2+ desensitization of the actin-myosin system, excess Ca2+ concentrations, calpain I activation, troponin degradation, ventricular dysfunction, and BNP secretion are observed.

Purpose
To evaluate association between apelin-12 and N-terminal pro-brain natriuretic peptide in STEMI patients depending on reperfusion injury.

Methods
In this study we included hundred patients with following criteria: chest pain lasting for more than 30 minutes, a 12-lead ECG characterized with ST-segment elevation in at least two contiguous leads ≥2.5 mm in men &lt;40 years, ≥2mm in men ≥40 years, or ≥1.5 mm in women in leads V2-V3 and/or ≥1 mm in other leads, rise of cardiac troponin I, and patients who have undergone primary percutaneous coronary intervention (PCI) within period of 12h. The levels of apelin-12, creatine kinase (CK), the MB fraction of creatine kinase (CKMB), troponin I, NT-proBNP, CRP, and other routine laboratory parameters were measured.

Results
In patients with TIMI flow ≤2 the median of apelin-12 level was 1.94 (0.26-8.88), and with TIMI flow 3, it was 2.42 (0.49-10.90). Variability was observed in the apelin values (Mann-Whitney test) based on TIMI flow grade (p&lt;0.010), and in the the N-terminal pro-brain natriuretic peptide (p&lt;0.031) (Table 1). The degree of association between apelin-12 and NT-proBNP was analyzed with Pearson’s correlation resulting in patients without reperfusion injury (TIMI flow 3).
p= -0.042, while in those with reperfusion injury (TIMI flow ≤2) p= -0.25. Figure 1 shows the association of apelin-12 and NT-proBNP in patients with TIMI flow grade 3, while Figure 2 this association shows in patients with TIMI flow grade ≤2.Conclusions: Apelin-12 levels inversely correlated with N-terminal pro-brain natriuretic peptide levels depending reperfusion injury.
This confirms the predictive value of Apelin for reperfusion injury which may lead to contractile myocardial dysfunction increasing level of NT-proBNP.
Examining factors associated with social participation in Adults with Congenital Heart Disease (ACHD)
Authors: Siyah T , Topcuoglu C , Vardar Yagli N , Calik Kutukcu E , Aykan H H , Ertugrul I , Karagoz T , Saglam M 
Published: June 2024

Abstract

Background/Introduction
Challenges encountered in the treatment and management of the disease, along with social and physical limitations, recurrent treatments and surgical interventions, future health concerns, and the lifelong need for follow-up, can impact the lives of individuals with ACHD (1). This impact may restrict the effective social and occupational inclusion, relationship and active participation in society of individuals with ACHD in the dimension of social participation.

Purpose
The aim of our study was to examine factors related to social participation in the ACHD population.

Methods
In our study, the Community Integration Questionnaire (CIQ) was used to evaluate participation. The CIQ consists of sub-dimensions of domestic participation, social participation, and participation in productive activities. A high score on the questionnaire indicates a high level of social participation. Additionally, the 6-Minute Walk Test (6MWT) was used for functional capacity assessment, digital dynamometer for muscle strength assessment, and Jamar dynamometer for hand grip strength. The Fatigue Severity Scale, International Physical Activity Questionnaire (IPAQ), Multidimensional Quality of Life Scale, Physical Activity Barrier Scale and Depression-Stress-Anxiety Scales were also assessed.

Results
In our study, 42 participants were included, comprising 20 females with a mean age of 27.05±8.97 years and 22 males with a mean age of 22.41±4.45 years. A moderate positive correlation was found between the CIQ total score and the 6-MWT (r=0.364; p=0.021) and Multidimensional Quality of Life (r=0.441; p=0.003), while a moderate negative correlation was observed with the Physical Activity Barriers Scale (r=-0.310; p=0.046). Additionally, a moderate positive correlation was identified between the CIQ-Social Participation and knee extension muscle strength (r=0.412; p=0.007) and IPAQ (r=0.452; p=0.003), and a moderate negative correlation was found with Depression (r=-0.466; p=0.002) and Stress (r=-0.330; p=0.035).

Conclusion(s)
Considering the associated factors such as quality of life, physical activity barriers, muscle strength, physical activity, depression, and stress, supporting social participation is a crucial component of comprehensive healthcare for individuals with ACHD.
In Silico TRials guide optimal stratification of ATrIal FIbrillation patients to Catheter Ablation and pharmacological medicaTION: the i-STRATIFICATION study
Authors: Dasí Albert , Nagel Claudia , Pope Michael T B , Wijesurendra Rohan S , Betts Timothy R , Sachetto Rafael , Loewe Axel , Bueno-Orovio Alfonso , Rodriguez Blanca 
Published: June 2024

Abstract

Aims
Patients with persistent atrial fibrillation (AF) experience 50% recurrence despite pulmonary vein isolation (PVI), and no consensus is established for secondary treatments. The aim of our i-STRATIFICATION study is to provide evidence for stratifying patients with AF recurrence after PVI to optimal pharmacological and ablation therapies, through in silico trials.

Methods and results
A cohort of 800 virtual patients, with variability in atrial anatomy, electrophysiology, and tissue structure (low-voltage areas, LVAs), was developed and validated against clinical data from ionic currents to electrocardiogram. Virtual patients presenting AF post-PVI underwent 12 secondary treatments. Sustained AF developed in 522 virtual patients after PVI. Second ablation procedures involving left atrial ablation alone showed 55% efficacy, only succeeding in the small right atria (&lt;60 mL). When additional cavo-tricuspid isthmus ablation was considered, Marshall-PLAN sufficed (66% efficacy) for the small left atria (&lt;90 mL). For the bigger left atria, a more aggressive ablation approach was required, such as anterior mitral line (75% efficacy) or posterior wall isolation plus mitral isthmus ablation (77% efficacy). Virtual patients with LVAs greatly benefited from LVA ablation in the left and right atria (100% efficacy). Conversely, in the absence of LVAs, synergistic ablation and pharmacotherapy could terminate AF. In the absence of ablation, the patient’s ionic current substrate modulated the response to antiarrhythmic drugs, being the inward currents critical for optimal stratification to amiodarone or vernakalant.

Conclusion
In silico trials identify optimal strategies for AF treatment based on virtual patient characteristics, evidencing the power of human modelling and simulation as a clinical assisting tool.