bluuebunny/crossref_metadata_2025_split huggingface dataset:
New protein biomarkers associated with risk of myocardial infarction in women: the CorFemina project
Authors: De Martin T V , Saether J C , Langaas M , Bye A 
Published: June 2024

Abstract

Background
The burden of cardiovascular disease (CVD) is extremely large in terms of morbidity and mortality worldwide, and it is the leading cause of death in women. Several traditional CVD risk factors are modifiable through lifestyle interventions and medical therapy, and thus, early identification of risk is of great importance to prevent CVD. However, current CVD risk prediction models fall short in risk stratification, particularly for women. Therefore, the discovery of new CVD biomarkers holds the promise to improve the prediction of CVD risk in women.

Purpose
This pilot study aimed to identify new protein biomarkers associated with risk of myocardial infarction (MI) in women.

Methods
The study adopted a retrospective nested case-control design with incidence of MI as endpoint during a 5-year follow-up. Cases and controls were drawn from women (45-74 years old) with a low 10-year risk of acute MI calculated using the NORRISK2 model and available serum samples in the Trøndelag Health study (HUNT) biobank. Using registry data, 24 cases that experienced MI or coronary event requiring percutaneous coronary intervention were selected, and 25 age-matched women that remained CVD-free served as controls. The Olink Cardiometabolic panel II was used to quantify 96 proteins in serum samples. Differences between case and control groups were tested using a two-sample t-test at nominal significance level .05 for every protein and the results were corrected for multiple testing using the Benjamini-Hochberg method (controlling the false discovery rate, FDR).

Results
In total, 10 protein biomarkers had a nominal significant lower concentration in cases compared to controls. Differences were observed in biomarkers of inflammation (i.e., interleukin 18, interleukin 27, interleukin-1 receptor-like 2, lymphotactin), as well as in proteins associated with atherosclerosis, extracellular matrix remodelling, cell proliferation, plaque progression and instability (i.e., matrilysin, dickkopf-related protein 1, bone morphogenetic protein 6). We found a dysregulation in V-set and immunoglobulin domain-containing protein 2, a transmembrane protein with immunosuppressive properties, and alpha-L-iduronidase, an essential enzyme for the breakdown of glycosaminoglycans (GAGs). Accumulation of GAGs has previously been linked to atherosclerosis, clot formation, and myocardial fibrosis. However, none of the biomarkers was significantly different between groups after adjustment for multiple testing (adjusted FDR, p=.293). Results are presented in Figure 1 and 2.

Conclusions
Several protein biomarkers were significantly different at baseline between women that had a cardiovascular event within a 5-year follow-up and women that remained healthy. These biomarkers point toward a pivotal role of inflammation and immune dysregulation in CVD pathway in women. The differences were not significant after adjustment likely owing to the small sample size of this pilot study.
Intima-media thickness measured at the common carotid artery, carotid bifurcation, and internal carotid artery in cardiovascular risk assessment
Authors: Seekircher L , Tschiderer L , Willeit P 
Published: June 2024

Abstract

Background
Current guidelines recommend measuring carotid intima-media thickness (IMT) at the common carotid artery (CCA), because these measurements are considered to have a higher precision and reproducibility than IMT values assessed at the carotid bifurcation (BIF) or the internal carotid artery (ICA). However, available evidence from prospective cohort studies on the association with disease risk is conflicting.

Purpose
We aimed to reliably quantify associations of CCA-, BIF- and ICA-IMT with the risk for atherosclerotic cardiovascular disease and their added predictive values.

Methods
We analysed participant-level data of 20 prospective studies from the Proof-ATHERO consortium. We pooled study-specific hazard ratios for cardiovascular disease (CVD, defined as coronary heart disease or stroke) using random-effects meta-analysis.

Results
Individual records were available for 47,358 participants. The mean age was 56 years (standard deviation [SD] = 11), 49% were female, 10% had a history of CVD, 7,115 CVD events were recorded, and the median follow-up was 6.1 years. Mean IMT baseline values were 0.80 mm (SD 0.25) at the CCA, 1.04 mm (SD 0.44) at the BIF, and 0.86 mm (SD 0.42) at the ICA and differed by a mean of 0.07 mm (95% confidence interval [CI]: 0.03-0.10 mm; P&lt;0.001) between CCA and ICA, 0.26 (0.21-0.32, P&lt;0.001) between CCA and BIF, and 0.20 (0.17-0.23, P&lt;0.001) between BIF and ICA. Correlation coefficients between segment-specific IMT values were moderately strong (CCA-BIF: 0.47 [95% CI: 0.43-0.51]; BIF-ICA: 0.49 [0.42-0.55]; CCA-ICA: 0.39 [0.34-0.44]). CCA-, BIF- and ICA-IMT were approximately linearly associated with CVD risk. Hazard ratios per SD higher IMT were 1.20 (95% CI: 1.15-1.26; I²=36.2%) for CCA-IMT, 1.20 (1.12-1.28; I²=65.5%) for BIF-IMT, and 1.16 (1.11-1.21; I²=32.4%) for ICA-IMT when adjusted for age, sex, and history of CVD and did not differ significantly between the three segments (CCA-BIF: P=0.775; CCA-ICA: P=0.077; BIF-ICA: P=0.134). In a multivariable adjusted model, hazard ratios attenuated to 1.15 (1.13-1.18) for CCA-IMT, to 1.11 (1.04-1.19) for BIF-IMT, and to 1.12 (1.10-1.15) for ICA-IMT but remained statistically significant. Adding IMT at all three segments to a model containing conventional CVD risk factors provided a greater C-index improvement than adding IMT at one segment only (+0.0071 vs. +0.0056 for CCA-IMT [P&lt;0.001] or +0.0053 for BIF-IMT [P&lt;0.01] or +0.0038 for ICA-IMT [P&lt;0.001].

Conclusion
The associations of CCA-, BIF- and ICA-IMT with incident CVD were positive, approximately linear, and similarly strong. Improvement in risk discrimination was highest when IMT was measured at all three segments.
Optimization and validation of high, intermediate and low risk cut-off points in risk functions for primary cardiovascular prevention. The ORESTES project
Authors: Herrera Marin N , Subirana I , Camps-Vilaro A , Palomo I , Sanchis J , Serrano J , Tizon-Marcos H , Degano I R , Garcia-Lledo A , Gil M , Marrugat J 
Published: June 2024

Abstract

Background
Medical societies recommend strategies based on the identification of high-risk individuals using mathematical functions that provide risk scores for ischemic heart disease (IHD) or cardiovascular disease (CVD) at 10 years or more. Each function suggests its cut-off points (generally multiples of 5) that classify patients into low, intermediate and high/very high-risk levels. The proportion of general population classified in the low-, intermediate- and high-risk groups may vary significantly depending on the risk function used. Therefore, we postulate that cut-off points can be setup in such a way that the distribution of the population (percentile distribution) among the risk groups is the same regardless of the risk function.

Purpose
To determine the risk cut-off points that produce the same population distribution in the low (65%), intermediate (20%) and high-risk (15%) categories, for the most commonly IHD and CVD scores: Framingham IQ, REGICOR-IHD, FRESCO-IHD, SCORE2, FRESCO-CVD, CUORE and AHA. And to compare and evaluate their performance according to the proposed percentile distribution cut-off points.

Methods
We used a population-based cohort of 816,834 residents aged 45 to 74 years in Catalonia, Spain, with a median of a following-up greater than 10 years including fatal and non-fatal cardiovascular events and all-cause fatal events. Individuals baseline characteristics, i.e. age, sex, cholesterol, diabetes, smoking status, blood pressure and lipid-lowering and hypertension treatments, were obtained from the Primary Care Center Registries. Fatal and non-fatal events were obtained from Mortality and Hospital discharge records, respectively. The number of individuals with complete data was 437,734. The cut-off points were calculated using the percentile distribution. Performance and concordance of the risk functions are assessed by the categorical Net Reclassification Index (cNRI) and the Number Needed to Treat (NNT), and by Kappa index, respectively.

Results
Table 1 shows the cut-off points in the risk (%) of IHD and CVD necessary to obtain an equivalent population distribution of 65% at low risk, 20% at intermediate and 15% at high risk with the considered functions (percentile cut off-points), and the performance measurements (cNRI and NNT). Table 2 shows the pairwise Kappa index in assigning individuals in one of the three risk groups defined by the percentile cut-off points.

Conclusions
The ORESTES project successfully establish cut-off points in the risk of IHD and CVD calculated using 7 risk functions commonly used in Europe, which define equivalent population groups for low, intermediate and high risk.
The Relationship between updated Systemic Coronary Risk Estimation (SCORE 2) and markers of subclinical atherosclerosis and target organ damage in asymptomatic population with metabolic syndrome
Authors: Kostic S , Djordjevic D , Deljanin Ilic M , Tasic I , Stoickov V 
Published: June 2024

Abstract

The updated SCORE algorithm (SCORE2) estimates an individual’s 10-year risk of fatal and non-fatal CVD events (myocardial infarction, stroke) in apparently healthy people aged 40-69 years with risk factors that are untreated or have been stable for several years.

Aim of study
This study evaluated the association between SCORE 2 and markers of subclinical atherosclerosis and target organ damage in asymptomatic patients with metabolic syndrome (MetSy).

Method
The study included 131 participants, without manifested cardiovascular disease. The patients were divided into 2 groups. The first group (I) consisted of subjects with MetSy, n=67 (age: 53,5 ± 8,00), the second (II) group is control, without MetSy, n=64. For all patients was determined: presence of risk factors for cardiovascular disease (hypertension, hyperlipidaemia, smoking, diabetes, obesity, age), SCORE and SCORE 2, laboratory analysis, anthropometric measurements, fatty liver index (FLI), microalbuminuria, echocardiographic examination, carotid ultrasound (with measurement intima-media thickness (C-IMT), analysis carotid atherosclerotic plaques), exercise stress testing.

Results
Subjects with MetSy had a higher average number of risk factors, SCORE and SCORE 2 level (p&lt;0,0001), body mass index (p&lt;0,0001), FLI (p&lt;0,0001), more often present fatty liver (83 vs. 21%, p&lt;0,0001). C-IMT were significantly higher in the group with MetSy (0,80 ± 0,20 vs. 0,60 ± 0,09, p&lt;0,0001). The high C-IMC values (≥0.90) were observed in 26% patients with MetSy, p&lt;0,0001. Patients with MetSy had more frequently one or more carotid plaques (p&lt;0,0001), higher average number of carotid plaques (p = 0,01) and percentage of stenosis (p=0,001). In MetSy group plaques were mostly fibrocalcified (28%), followed by fibrous (22%) and calcified, in non MetSy group were fibrous (14%). Subjects with MetSy had a higher average left ventricular mass (p=0,001); more frequently had diastolic dysfunction (p&lt;0,0001) and left atrial dilation (p&lt;0,0001); 9 subjects (15 %) from the I group had a positive stress test. There was no difference in the frequency of microalbuminuria between the two groups. There is a correlation between SCORE 2 and very high risk level with carotid intima-media thickness and carotid plaques (p&lt;0,0001), left ventricular mass (p=0,01), diastolic dysfunction (p&lt;0,0001), microalbuminuria (p=0,03) and positive stress test (p=0,01). Multivariable logistic regression analysis showed that SCORE 2 was associated with presence of carotid plaques and C-IMT (95 % CI 0,007-0,019; p&lt;0,001).

Conclusion
Our study showed a significant association between the SCORE 2 and markers of subclinical atherosclerosis and target organ damage in asymptomatic population with metabolic syndrome.
Laboratory parameters associated with elevated coronary artery calcium burden in patients with newly diagnosed type 2 diabetes mellitus
Authors: Bakalli A , Hyseni V , Gjikolli B , Krasniqi X , Elezi S 
Published: June 2024

Abstract

Introduction
Cardiovascular complications are not exclusive to long-standing diabetes mellitus (DM); newly diagnosed type 2 diabetes mellitus (NDT2DM) may also be associated with cardiac problems, although this aspect has been less thoroughly explored. The computed tomography calcium score (CTCS) in the coronary arteries has become a widely available, accurate, and dependable tool for determining the risk of major cardiovascular events, particularly in asymptomatic individuals. Individuals with DM are expected to undergo regularly routine laboratory examinations.

Purpose
The objective of this study was to determine the laboratory parameters related to occurrence of subclinical atherosclerotic plaques in coronary arteries, as detected by Computed Tomography (CT), in patients with NDT2DM.

Methods
In this prospective cross-sectional study 101 patients with NDT2DM, according to the criteria of the American Diabetes Association, were included. CTCS was performed on all patients by 64-slice cardiac CT, with a thickness of 2-5 mm. Calcification was identified as a structure &gt;1 mm attached to or located within the lumen of a coronary vessel with intensity &gt;130 HU. The Agatston method was used to determine the CTCS. Patients were categorized into five groups based on their calcium levels (0, 0-.
10, 11-100, 101-400 and &gt;400), and all obtained parameters were subsequently compared between the five groups. With Spearman’s correlation test we also analyzed the relationship between laboratory parameters and the level of CTCS. Exclusion criteria were: stable angina pectoris, acute coronary disease, severe anemia, patients with history of stroke, moderate/severe renal insufficiency, liver insufficiency, claustrophobic patients, and pregnant women.

Results
Of the 101 asymptomatic patients with NDT2DM, 53 (52.5%) were males, with mean age of 54.4 ± 11.6 years and mean duration of diabetes of 2.8 ± 5.3 months. In table 1 the differences between the 5 groups regarding laboratory parameters are presented. Statistical significance is shown for erythrocyte sedimentation rate (ESR) (P=0.044). With Spearman's correlation, we obtained a significant correlation between the CTCS and the following laboratory parameters: ESR [r= 0.280 (95% CI 0.083-0.455), P=0.0046] and triglyceride level [r= 0.196 (95% CI -0.005 - 0.382), P=0.049].

Conclusions
Individuals diagnosed with NDT2DM who exhibit elevated erythrocyte ESR and triglyceride levels may be susceptible to an increased burden of coronary artery calcium. Consequently, these patients should undergo careful management, focusing on both glycemic control and cardiovascular prevention. Comparison between the five groups.
Real-world evaluation of performance and practical utility of multi-biomarker risk report for cardiovascular and other chronic diseases
Authors: Kerminen S 
Published: June 2024

Abstract

Introduction
Identifying individuals at high risk for cardiovascular disease (CVD) and other chronic diseases is the key to most effectively use targeted preventative interventions to reduce individual disease risks and the burden on the healthcare system. In current clinical practice, risk estimation is based on calculators like SCORE2 require information from multiple sources (physical measurements and questions). Estimating risk of other diseases (e.g. diabetes or liver disease) requires separate calculators that require non-overlapping inputs. Thus multi-disease risk prediction is rarely deployed at scale.

Purpose
To improve the accuracy and efficacy of primary prevention in clinical practice, we developed and tested a risk report that is based on biomarkers from a single blood sample, age and sex, and estimates risks for 8 chronic diseases.

Methods
To identify disease risks, we utilise nuclear magnetic resonance (NMR) spectroscopy to measure 39 clinically validated metabolic biomarkers from a single blood sample. We trained multi-biomarker risk scores (including age and sex) for CVD, myocardial infarction (MI), type two diabetes, chronic kidney disease, and 2 liver and 2 lung diseases using over 60,000 samples from UK Biobank and tested score performance on a separate testing set as well as independent data from two other large biobanks. We designed a report that shows both an individual’s absolute risk and relative risk compared to others of their sex and age for all 8 diseases. To enable large-scale usage in healthcare, we implemented an automated protocol for blood sample measurements, generating and returning the risk reports, and obtained regulatory approval. During an implementation pilot in Finnish clinics we assessed the quality of returned results and collected feedback from healthcare professionals.

Results
For all diseases, the performance of multi-biomarker scores was similar to or better than the selected existing risk tool. E.g., for MI, multi-biomarker score resulted an AUC of 0.72 (0.71-0.73, 95% confidence interval) while the national risk calculator for MI, FINRISK 2.0, showed AUC of 0.73 (0.72-0.74). A total of 185 patients participated in the implementation pilot. The results of the quality assessment of biomarker concentrations and disease risks demonstrated a good concordance with the expected values and rates from population specific research cohorts. According to feedback obtained from the healthcare professionals, the risk report was deemed clear and understandable, as well as easy to communicate with patients. These reports have now been adopted in routine use for nation-wide occupational health screens with a Finnish private healthcare provider.

Conclusions
We presented a real-world application for preventative health care to assess disease risk for 8 common chronic diseases in one go and demonstrated its performance and feasibility for large-scale risk assessment in a clinical setting.
Air pollution associates with poor mental health and amplifies the premature cardiovascular death in the United States: longitudinal nationwideanalysis
Authors: Abohashem S , Aldosoky W , Civieri G , Goudot G , Dar T 
Published: June 2024

Abstract

Background
While air pollution (i.e., particulate matter with aerodynamic diameter ≤2.5mm-PM2.5) and poor mental health (PMH) are linked to premature all-cause mortality, their interrelationship and joint impact on premature cardiovascular mortality (PCVM) in the United States, is unknown.

Purpose
Herein we sought to test the hypothesis that high exposure to PM2.5 associates with heightened PMH and an amplified PCVM risk related to PMH.

Methods
We analyzed annual PM2.5 levels and average PMH (days) data from the Center for Disease Control and Prevention (CDC) PLACES databases across 3047 U.S. counties. PM2.5 exposure was dichotomized (high/low) per World Health Organization standards; PMH was categorized into tertiles. Age adjusted PCVM rates (&lt;65 years of age) were obtained from the CDC WONDER databases. County characteristics were sourced from County Health Rankings project. Using generalized linear mixed models with gamma distribution, we calculated rate ratios (RR).

Results
Among 315,720,938 residents lived in 3047 counties in 2013, 1,079,656 (0.34%) PCVM deaths recorded during study period (2013-2019). In the fully adjusted analyses*, high PM2.5 associated with elevated PMH (RR [95%CI]: 1.10 [1.08, 1.11], p&lt;0.001]. In counties with high PM2.5 (≥10 µm2), PMH (T3 vs. T1) associated with a 3-fold increase in PCVM (RR: 1.15 [1.12, 1.18]) compared to low PM2.5 (1.05 [1.01, 1.08]), with p interaction &lt;0.001. This trend persisted across PCVM subtypes (Figure1).

Conclusion
High PM2.5 worsens PMH, significantly amplifying the PCVM burden across the United States, beyond other social determinants of health. Targeted public health strategies must urgently address the interconnected pollution-mental health crisis to mitigate rising PCVM.
Potentially avoidable hospitalizations for hypertension in Switzerland
Authors: Maung K , Marques-Vidal P E D R O , Gouveia A L E X 
Published: June 2024

Abstract
We assessed the trends, characteristics. and consequences of potentially avoidable hospitalizations (PAH) for hypertension in Switzerland, for period 1998 to 2018. Hospital discharge data from the Swiss federal office of statistics. Hospitalizations with hypertension as the main cause for admission were eligible. PAH for hypertension was defined according to the Organization for Economic Cooperation and Development criteria. Overall, data from 117’507 hospitalizations (62.1% women) was used. The number of PAH increased between 1998 (n=1685) and 2018 (n=3410), and their frequency among hospitalizations for hypertension increased from 36.9% in 2008 to 73.0% in 2018. Compared to non-PAH, patients with PAH for hypertension were younger, more frequently women (66.9% vs. 56.7%), non-Swiss nationals (15.9% vs. 10.9%), were more frequently admitted as an emergency (78.9% vs. 59.5%), and by the patient’s initiative (33.1% vs. 14.1%). Patients with PAH had also less comorbidities, as per the Charlson’s index. Patients with PAH for hypertension were more frequently hospitalized in a semi-private or private setting, stayed less frequently in the ICU (4.6% vs. 7.3%), were discharged more frequently home (91.4% vs. 73.0%), and had a shorter LOS than patients with non-PAH for hypertension: median and [interquartile range] 5 [3-8] vs. 9 [4-15] days. In 2018, the total costs of PAH were estimated at 16.5 million CHF, corresponding to a median cost of 4936 (4445-4961] CHF per stay. We conclude that in Switzerland, PAH represent a considerable fraction of hospitalizations for hypertension, and carry a non-negligible health cost.