bluuebunny/crossref_metadata_2025_split huggingface dataset:
Acute electrophysiological effects of energy drink, energy gum and coffee: a double-blind randomized placebo-controlled crossover study
Authors: Alviar C , Lapierre S , Soonhuae C , Leong M C , Yan X , Ruzieh M , Handberg E , Christou D 
Published: November 2023

Abstract

Background
Energy drink consumption is highly prevalent in young adults, especially in males, and has been associated with adverse cardiovascular events, including QT prolongation and atherothrombosis. A proposed mechanism underlying these adverse cardiovascular effects is caffeine, but this has not been systematically evaluated. Therefore, the purpose of this study was to compare the acute electrophysiological effects of energy drink consumption with other forms of caffeine consumption in young males.

Methods
We performed a randomized, double-blind, placebo-controlled, crossover study in 16 young healthy males. Each participant underwent electrocardiography assessment at pre- and post-treatment (1-hour and 2-hours) in response to 4 beverage and gum combinations: 1) energy drink + placebo gum (ED); 2) coffee + placebo gum (C); 3) placebo beverage + caffeinated energy gum (EG); and 4) placebo beverage + placebo gum (P). Caffeine content was the same in all treatment combinations and a washout period of at least 1-week was allowed among treatments.

Results
At 1-hour post-treatment, heart rate increased in response to ED while it decreased in response to EG (p&lt;0.05 for ED vs. EG; Figure 1A). At 2-hours post-treatment, the increase in heart rate after ED and Coffee was significantly greater compared to the change in heart rate in response to the other treatments (p&lt;0.05). The increase in QRS duration 1-hour post-treatment was significantly greater after ED compared to EG and Placebo (p &lt;0.05). Corrected QT (QTc) duration was significantly reduced at 1-hour post-treatment in response to EG vs. ED (p&lt;0.05), but was not different compared to the other treatments. At 2-hours post-treatment, QTc duration was significantly reduced in response to EG and was increased in response to Coffee (p &lt; 0.05 for EG vs. ED and C, Figure 1C). The most prominent increase from baseline in the percentage of participants experiencing ventricular ectopy was in response to ED (Figure 1D).

Conclusions
The acute electrophysiological effects of energy drink, energy gum and coffee do not appear to be mediated by caffeine content. Further investigations are warranted to better understand the cardiovascular effects of these caffeinated products.
Comparing electrophysiological biomarkers and circulating cardiac biomarkers in predicting cardiovascular mortality and all-cause mortality in the akershus sleep apnea (ASAP) epidemiological cohort
Authors: Nahoui H , Feng X , Oeverby T C , Sigurdardottir F D , Hrubos-Stroem H , Omland T , Einvik G , Nikkonen S , Leppaenen T , Arnardottir E S , Toeyraes J , Myllymaa S 
Published: November 2023

Abstract

Background
Major cardiovascular events (MACE) and mortality in obstructive sleep apnea (OSA) patients have been frequently reported. However, there is an ongoing debate regarding biomarkers predicting MACE and mortality in OSA. The Apnoea Hypopnea Index (AHI) has been used to assess the severity of Obstructive Sleep Apnea (OSA) despite poor association with adverse outcomes in OSA patients. Novel electrophysiological biomarkers (EPBs) such as desaturation parameters have been suggested as an alternative, and have been reported to be stronger predictors of cardiovascular mortality and heart failure. However, circulating cardiac biomarkers (CCBs) remain strong predictors of mortality and cardiovascular disease in the general population.

Purpose
To detect the incidence of MACE and all-cause mortality after a median of 13.8 years follow-up in individuals with OSA, and to assess the ability of CCBs and EPBs to predict MACE and all-cause mortality.

Methods
Polysomnography and CCB analyses (cardiac troponin I (cTnI) and T (cTnT)) were conducted in 459 participants in the Akershus Sleep APnea study (ASAP) between 2006-2008. EPBs evaluated were the AHI, oxygen desaturation index (ODI), desaturation duration (DesDur) and desaturation severity (DesSev). Cox regression and cumulative incidence Kaplan-Meier curves were used for survival analysis. Comparison of EPBs and CCBs in predicting MACE and all-cause mortality was assessed by the area under the curve (AUC).

Results
77 and 35 participants reached the endpoint of MACE and all-cause mortality, respectively. In the adjusted cox regression model, cTnI and cTnT were significantly associated with MACE with a hazard ratios of 1.84 [95% Confidence interval [CI], 1.43, 2.37] and 1.52 [1.05, 2.20], respectively. Association of these CCBs with all-cause mortality was with a hazard ratios of 2.02 [1.38, 2.96] and 1.75 [1.05, 2.92], respectively. Moreover, cTnI had the highest AUC of 0.77 and 0.75 in predicting MACE and all-cause mortality. Notably, high AHI, ODI, DesDur and DesSev (upper quartile) increased the cumulative incidence of MACE and all-cause mortality in the subgroup of patients with high CCBs (upper quartile) compared to the subgroup of patients with high CCBs and low EPBs (lower quartile).

Conclusion
CCBs were more associated with all-cause mortality and MACE than EPBs in ASAP epidemiological cohort. However, the tested EPBs are important biomarkers that increase CCBs prediction of both MACE and all-cause mortality.
Lower 6-minutes walk test result and presence of cardiovascular risk factors linked to healthcare facility visits of pilgrims: the importance of fitness in hajj pilgrimage
Authors: Harsoyo P M , Ardiana M , Sufiyah I M , Hermawan H O , Rahma S 
Published: November 2023

Abstract

Background
Hajj pilgrimage, a mandatory religious practice for the Muslims, is a physical rite attributed heavily on the fitness of the participants due to increased workload in performing its activities. The 6-minutes walk test is a simple assessment to predict candidates’ fitness level.

Objective
We sought to determine the association between pilgrim candidate fitness level, determined by 6-minutes walk test result during predeparture preparation, as well as pre-existing potential risk factors of hajj pilgrim participants.

Method
In this retrospective cohort, we obtained the data of 2022 pilgrimage participants from Indonesian Ministry of Religious Affairs, consisting of demographic characteristics, anthropometric indexes, medical history, physical examination, and functional exercise capacity predicted by 6-minute walk test conducted during pre-departure preparation. Baseline demographic, bivariate tests for each variable, and multivariate test were analyzed by IBM SPSS 26.

Result
There was significant correlation between age of ≥60 (p &lt; 0.001), hypertension (p &lt; 0.001), diabetes mellitus (p &lt; 0.001), 6-minutes walk test (p &lt; 0.001), smoker status (p = 0.008), high LDL-C (p = 0.026), obesity (p =0.033), female sex (p = 0.043) and healthcare visit episode of pilgrims. The risk ratio value for low result group of 6-minutes walk test (&lt; 500 meters) against outpatient incidence during hajj period was 1.08 (95% CI; 1.04 -1.12). It indicated that the inability of reaching &gt;500 meters in 6-minutes walk test is related to outpatient incidence by 1.08 times.

Conclusion
There is a slight increase in healthcare visit incidence in pilgrims with low result of 6-minutes walk test. The 6-minutes walk test, a simple and reproducible assessment of fitness level, may provide useful information to improve preparation of pilgrimage.
Coronary artery calcification score and 19 biomarkers on cardiovascular events; a 10-year follow-up DanRisk substudy
Authors: Schaeffer M , Rasmussen J H , Fredgart M H , Hasific S , Steffensen F H , Lambrechtsen J , Sand N P R , Rasmussen L M , Diederichsen A C P 
Published: November 2023

Abstract

Background
SCORE2 is recommended for the estimation of the 10-year risk of cardiovascular disease (CVD), and guideance of medical therapy. However, the prediction is deficient. Coronary artery calcification (CAC) score has been proven to improve the risk assessment in primary prevention of CVD, however, it is also resource-intensive. Biomarkers may be an advantageous alternative.

Purpose
This study aims to determine and compare the additive value of CAC-score and 19 biomarkers in risk prediction.

Methods
Classic cardiovascular (CV) risk factors, CAC-score, and a wide range of blood samples (including lipids, calcium-phosphate metabolism, troponin, inflammation, and kidney function), were collected from 1,211 randomly selected middle-aged men and women in this multicentre prospective cohort in 2009-2010. 10-year follow-up data on CV-events (death from CVD, stroke, myocardial infarction, heart failure or coronary artery revascularization) were obtained from the Danish Health Registries. The association between SCORE2, CAC-score, biomarkers, and CV-events was displayed in Kaplan Meier diagrams, assessed using cox proportional hazard rates (HR) and compared using area under the curve (AUC) calculation of receiver operating characteristic (ROC) curves. The net reclassification improvement (NRI) for CAC-score compared to SCORE2 was also calculated.

Results
92 participants had CV-events. Events were seen in 29.3% of 41 participants with a very high risk (SCORE2 ≥10%) and 24.2% of 66 participants with CAC-score ≥400. Adjusted for risk factors, CAC-score was significantly associated with events adjusted HR 1.91 (95%CI: 1.10;3.31), 3.61 (95%CI: 1.93;6.76), and 5.2 (95%CI: 2.63;10.29) for CAC-score 1-99, CAC-score 100-399 and CAC-score ≥400, respectively. HR for the highest quartile of C-reactive protein (CRP) was 2.34 (95%CI: 1.15;4.47), while none of the remaining biomarkers improved HR.
CAC-score improved AUC of the SCORE2 model (AUC_CAC+SCORE2: 0.72, AUC_SCORE2: 0.67, p&lt;0.01) as seen in Figure 1. A combination of selected biomarkers (total cholesterol, low-density lipoprotein, phosphate, troponin I, CRP, and creatinine) borderline improved AUC (AUC_Biomarkers+SCORE2: 0.71, AUC_SCORE2: 0.67, p=0.06).
Inclusion of CAC-score in the SCORE2 model improved the risk prediction. For participants with a CV-event, 73.9% had increased probabilities and 26.1% had decreased probabilities, compared to 42.4% increased and 57.6% decreased probabilities for participants without an event. NRI was 63% (p&lt;0.0001)

Conclusion
CAC-score remained to improve the prediction of CV-events, while the selected biomarkers did not.ROC of SCORE2 versus CAC-score+SCORE2
Comparison of SCORE and SCORE2 in determination rates with very high cardiovascular risks
Authors: Demirci D , Ersan Demirci D , Gerald C , Guven A Z , Elhan A H , Gibson C M 
Published: November 2023

Abstract

Background
Appropriate risk stratification is fundamental for cardiovascular disease (CVD) prevention. The European Society of Cardiology recently updated the Systematic Coronary Risk Estimation (SCORE) algorithm to SCORE2 for estimating the 10-year risk of first-onset CVD among Europeans. However, the performance of SCORE2 has not been examined in the non-European population.

Purpose
This study aimed to compare the results of CVD risk assessments between the SCORE and SCORE2 algorithms.

Methods
A total of 1089 non-diabetic patients who experienced their first episode of acute coronary syndrome (ACS) were included in the study. CVD risks were evaluated according to the SCORE charts based on age, sex, smoking status, blood pressure, total cholesterol, high-density lipoprotein cholesterol (HDL-C), and non-HDL levels.

Results
The SCORE2 algorithm identified 58.8% (n=640) of patients as very high risk, whereas the SCORE algorithm identified only 22.5% (n=245) of patients as such, demonstrating a statistically significant difference (p &lt; 0.001). Furthermore, there was a noticeable sex disparity in very high-risk classification between the two algorithms. Specifically, the SCORE algorithm identified a considerably higher proportion of males (25.7%; n=233) as very high risk compared to females (4.9%; n=12) (p &lt; 0.001). In contrast, the SCORE2 algorithm demonstrated a relatively smaller difference in the very high-risk category between males (59.7%; n=540) and females (54.3%; n=100) (p=0.181). A lower proportion of patients were classified as low to intermediate risk by the SCORE2 algorithm compared to the SCORE algorithm (3.9 % vs. 49.7%; p &lt; 0.001). On the other hand seven patients (0.6 %) aged between 70 to 73 years were reclassified from the very high-risk category by SCORE to the very high-risk category by SCORE2.

Conclusion
The study suggests that the SCORE2 algorithm is superior to the SCORE algorithm in classifying patients who developed first-onset ACS as very high risk. In the very high-risk category, the sex gap was less prominent using the SCORE2 algorithm than the SCORE algorithm. However, the SCORE2 algorithm may underestimate CVD risk levels among patients aged between 70 to 73 years.General characteristics of the patientsThe Comparison of CV risk levels
The association of lipoprotein(a) with patient characteristics and mortality in a primary prevention cohort: data from our clinic database
Authors: Cho L , Brennan D , Costa-Scharplatz M , Itani T , Nissen S 
Published: November 2023

Abstract

Background
Lipoprotein(a) [Lp(a)] has emerged as a causal risk factor for development of cardiovascular (CVD) and valvular heart disease. However, not much is known about the gender differences and Lp(a). The aim of our study was to investigate gender differences in clinical and laboratory characteristics of primary prevention patients with elevated Lp(a) and to study the associations between Lp(a) and all-cause mortality by gender.

Method
We analyzed data obtained from the Preventive Cardiology Information System (PreCis), a database of clinical and laboratory information on 8,136 consecutive primary prevention patients seen at our clinic preventive cardiology clinic from 1999-2018. Primary prevention was defined as having no history of coronary artery disease (CAD), coronary and peripheral arterial revascularization, nor atherosclerosis. Data regarding mortality were gathered from a combination of sources including the Social Security Death Index (SSDI), the Ohio State Department of Health Vital Statistics, and electronic medical record. All-cause mortality was assessed using time to event analyses, and adjusted Cox proportional hazards models. All statistical analyses were conducted using SAS version 9.4.

Result
In the overall cohort (n=8,136), 57% were female at a median age of 54 years and 43% were male at a median age of 52 years. Median Lp(a) was 24 (IQR 8-63) mg/dL in females and 18.6 (IQR 7-51) mg/dL in males. The proportion of females increased with increasing Lp(a) values from 54% with Lp(a) &lt;30 mg/dL to 69% with Lp(a) ≥90mg/dL. Female patients with Lp(a) ≥50 mg/dL were significantly more likely to have dyslipidemia (40.5% vs 34.1%; p&gt;0.001) and hypertension (27.3% vs 23.3%; p&gt;0.001) compared to &lt;50 mg/dL. There was a trend toward increased all-cause mortality in elevated Lp(a) group among female patients (&lt;50 mg/dL vs ≥50 mg/dL; (HR (95%CI): 1.22 (0.98-1.52); p=0.083).

Conclusion
In this primary prevention population, a higher proportion of females had elevated Lp(a) than males. Females with elevated Lp(a) presented with more comorbidities and a trend towards increased all-cause mortality. These findings suggest a gender difference in the distribution of Lp(a) and all-cause mortality in the primary prevention setting, which warrants further investigation.
Lipoprotein(a) is not a causal factor for the development of diabetes - a two-sample Mendelian randomization study
Authors: Lejawa M , Golawski M , Osadnik T , Jozwiak J , Gierlotka M , Lisik M , Pawlas N , Banach M 
Published: November 2023

Abstract

Introduction
The association between lipoprotein(a) [Lp(a)] and coronary artery disease is well known. Nevertheless, because physiological function of Lp(a) is not well understood, it is not clear what sort of adverse effects therapies aimed at Lp(a) reducing might have. One of the associations that was observed for the reduced Lp(a) levels was the increased incidence of diabetes. As genetic factors have a clear impact on Lp(a) levels, we applied Mendelian Randomization [MR] approach as a tool to determine the impact of Lp(a) on the risk of diabetes onset.

Purpose
To assess the impact of Lp(a) levels on the incidence of diabetes.

Methods
We conducted a two-sample MR study. Publicly available datasets were used as sources for summary statistics of genetic correlations. UK Biobank was the source of correlations for Lp(a) levels and FinnGen was used as the source of genetic correlations for type 2 diabetes. Only variants in the LPA gene region were utilized. Inverse-variance-weighted mean method was used for primary analysis. Secondary analyses were conducted by weighted median, mode, and MR-Egger methods. Sensitivity analyses were performed by leaving out random 30% of the variants as well as by using LPA gene variants that were previously published as significantly affecting Lp(a) levels.

Results
Data regarding genetic determinants of Lp(a) levels were available for 318922 participants, while summary statistics for type 2 diabetes were available for 49114 cases and 283207 controls. Primary analysis indicated that Lp(a) levels are not correlated with diabetes [p=0.362]. Genetic associations of included variants with Lp(a) levels (horizontal axis) and with type 2 diabetes mellitus (vertical axis) are presented in Figure. Secondary analyses were consistent with this finding [median p=0.100; mode p=0.156; MR-Egger p=0.243]. Selected variants did not show appreciable pleiotropy as indicated by MR-Egger intercept test [p=0.450]. Sensitivity analyses did not result in statistically significant findings [leave-30%-out analysis IVM p-values: 0.153-0.960].

Conclusions
Lp(a) levels determined by genetic background are not correlated with type 2 diabetes risks. This indicates that Lp(a) levels has likely no causal role in type 2 diabetes onset. This suggests that treatments aimed at reducing Lp(a) levels will not likely increase the risk of developing type 2 diabetes.
Hyperlipoproteinemia(a) in coronary artery disease patients: who are patients with very high levels and how do they respond to the PCSK9 antibody therapy?
Authors: Novakovic M , Trsan J , Krevel B , Cevc M , Fras Z , Jug B 
Published: November 2023

Abstract

Introduction
Lipoprotein(a) [Lp(a)] is a considerable risk factor for coronary artery disease [CAD] and a possible target for novel risk management therapy. On the one hand, increased Lp(a) levels may help select at-risk CAD patients who are better candidates for PCSK9 antibody therapy; on the other hand, PCSK9 antibody therapy has been shown to reduce Lp(a) levels.

Purpose
The aim of our study was two-fold: i) to appraise the prevalence and characteristics of CAD patients with elevated Lp(a), and ii) to identify possible predictors of Lp(a) levels reduction in CAD patients on PCK9 antibody therapy.

Methods
Consecutive patients with established CAD referred for cardiac rehabilitation from 2020 to 2022 were included and had Lp(a) serum levels measured using the Lp(a) assay on the RX Daytona+ automated biochemistry analyzer. Clinical and demographic predictors of Lp(a) &gt;50 mg/dL and &gt;100 mg/dL were assessed (namely age, sex and traditional risk factors). Furthermore, in patients with CAD and increased Lp(a) levels (&gt;100 mg/dL, which makes them eligible for full reimbursement of alirocumab or evolocumab as per national insurance policy), clinical and demographic predictors of Lp(a) levels reduction after 12 weeks of PCSK9 antibody therapy were assessed.

Results
We included 518 patients (average age 58 years, 21% females): 84 (16.2%) had Lp(a) levels &gt;100 mg/dL and 137 (26.4%) had Lp(a) levels &gt;50 mg/dL. Only the female sex was independently associated with increased Lp(a) levels &gt;100 mg/dL and &gt;50 mg/dL (32.1%, p=0.008 and 27.7%, p=0.030, respectively). In 57 patients on PCSK9 antibody therapy based on Lp(a) &gt;100 mg/dL, cigarette smoking and body mass index (BMI) were independent baseline-adjusted predictors of Lp(a) reduction after 3 months of PCSK9 antibody therapy; non-smokers had 27.5 mg/dL greater decrease in Lp(a) as compared to smokers (p=0.004), and BMI was associated with a decrease of 2.6 mg/dL per unit of BMI (p=0.020), respectively.

Conclusion
In patients with established CAD, the female sex is the only independent clinical predictor of increased Lp(a) levels, suggesting Lp(a) may be an important driver of CAD, especially in women. Conversely, Lp(a) reduction with PCSK9 antibody therapy was associated only with lifestyle risk factors (namely smoking and BMI), suggesting the possibility that lifestyle modification could improve response to treatment to PCSK9 inhibitors and should be researched further in prospective studies.
Impact of dilution on stochastically driven methanogenic microbial communities of hypersaline anoxic sediments
Authors: Font-Verdera Francisca , Liébana Raquel , Rossello-Mora Ramon , Viver Tomeu 
Published: November 2023

Abstract
Sediments underlying the solar salterns of S’Avall are anoxic hypersaline ecosystems dominated by anaerobic prokaryotes, and with the especial relevance of putative methanogenic archaea. Slurries from salt-saturated sediments, diluted in a gradient of salinity and incubated for &gt; 4 years revealed that salt concentration was the major selection force that deterministically structured microbial communities. The dominant archaea in the original communities showed a decrease in alpha diversity with dilution accompanied by the increase of bacterial alpha diversity, being highest at 5% salts. Correspondingly, methanogens decreased and in turn sulfate reducers increased with decreasing salt concentrations. Methanogens especially dominated at 25%. Different concentrations of litter of Posidonia oceanica seagrass added as a carbon substrate, did not promote any clear relevant effect. However, the addition of ampicillin as selection pressure exerted important effects on the assemblage probably due to the removal of competitors or enhancers. The amended antibiotic enhanced methanogenesis in the concentrations ≤ 15% of salts, whereas it was depleted at salinities ≥ 20% revealing key roles of ampicillin-sensitive bacteria.