bluuebunny/crossref_metadata_2025_split huggingface dataset:
The relationship between diabetes, obesity and cardiovascular disease phenotypes: a UK Biobank cohort study
Authors: Brown O , Drozd M , Mcgowan H , Giannoudi M , Conning-Rowland M , Gierula J , Straw S , Wheatcroft S B , Paradine K , Roberts L D , Levelt E , Ajjan R , Griffin K J , Kearney M T , Cubbon R M 
Published: November 2023

Abstract

Background
Obesity and diabetes mellitus (DM) frequently co-exist, yet their individual contributions to cardiovascular risk remain debated.

Purpose
We explored cardiovascular disease biomarkers, events and mortality in a large cohort stratified by body mass index (BMI) and DM. We hypothesised that DM with normal BMI is associated with a cardiovascular phenotype and event rate comparable to obesity without DM.

Methods
451,355 UK Biobank participants were stratified by ethnicity-specific BMI categories (normal, overweight, obese) and DM status. We examined cardiovascular biomarkers including: carotid intima-media thickness (CIMT); arterial stiffness; left ventricular ejection fraction (LVEF) and cardiac contractility index (CCI). Poisson regression models estimated adjusted incidence rate ratios (IRR) for myocardial infarction, ischaemic stroke and cardiovascular death, with normal weight non-DM as comparator. Correlation matrices of Poisson model’s coefficients were used to assess correlations between covariates.

Results
5% of participants had DM (10% normal weight, 34% overweight and 55% obese; versus 34%, 43% and 23%, respectively, in non-DM). In the non-DM group, overweight/obesity was associated with higher CIMT, arterial stiffness and CCI, and lower LVEF (p&lt;0.05); these relationships were diminished in the DM group. Within BMI classes, DM was associated with adverse cardiovascular phenotype (p&lt;0.05), particularly in the normal weight group. After 5,323,190 person-years follow-up, incident myocardial infarction, ischaemic stroke and cardiovascular mortality all rose across increasing BMI categories in the DM and non-DM groups (p&lt;0.05). However, normal weight DM had higher cardiovascular mortality than obese non-DM (IRR 2.81 [95% confidence interval: 2.24-3.54] vs IRR 1.84 [1.70-1.98]). Pairwise correlation analysis demonstrated the strongest correlates of cardiovascular parameters were markers of adiposity; this was apparent in the DM and non-DM groups, although these remained modest with Pearson’s correlation coefficients of no more than 0.25.

Conclusions
Obesity and DM are additively associated with adverse cardiovascular biomarkers and mortality risk. Whilst adiposity metrics are more strongly correlated with cardiovascular biomarkers than diabetes-oriented metrics, both correlate weakly, suggesting other factors underpin the high cardiovascular risk of normal-weight diabetes. Ideal target range for metrics of adiposity may therefore be lower than currently proposed in people with DM.Table 1:Adjusted IRR of CV deathFigure 1:KM Curve for CV death
Lipid core burden in relation to the severity of calcium burden assessed by computed tomographic coronary angiography in patients with chronic coronary syndrome
Authors: Nagamine T , Usui E , Hoshino M , Hada M , Hanyu Y , Ueno H , Nogami K , Matsuda K , Sayama K , Sakamoto T , Yonetsu T , Sasano T , Kakuta T 
Published: November 2023

Abstract

Background
Coronary calcium scores (CACS) obtained by computed tomographic coronary angiography (CTCA) enables a noninvasive assessment of coronary calcium burden both in a single vessel and in whole coronary tree. Although higher CACS in coronary tree is known as an atherosclerotic cardiovascular disease risk marker, coronary calcification is also known as a sign of plaque stabilization. Exploring the relationship between coronary calcification and lipid core burden may help understanding a role of calcium in coronary tree.

Purpose
We aimed to examine the relevance of lipid components assessed by near-infrared spectroscopy (NIRS) in accordance with different degrees of CACS assessed by preprocedural CTCA imaging.

Methods
We investigated consecutive patients who underwent elective percutaneous coronary intervention (PCI) and pre-PCI CTCA imaged within 3 months before PCI. Patients who had stents in target vessels and who required plaque modification before NIRS imaging were excluded. Target vessels were divided into tertiles based on target vessel CACS (CACSv) and total amount of 3-vessel CACS (CACSt), respectively. Lipid components of the target vessel were evaluated by maximum lipid core burden index in 4mm (maxLCBI4mm). MaxLCBI4mm was compared among the tertiles of CACSv and CACSt.

Results
A total of 95 target vessels in 95 patients were evaluated for the final dataset. CACSv categories were defined as follows: 1st tertile (CACSv &lt;66), 2nd tertile (CACSv &gt;66 and &lt;250), and 3rd tertile (CACSv &gt;250). CACSt categories were defined as showing CACSt &lt;190 (1st tertile), CACSt &gt;190 and &lt;700 (2nd tertile), and CACSt &gt;700 (3rd tertile). MaxLCBI4mm increased in proportion to an extent of CACv tertiles (306 [129-463], 280 [125-460], and 444 [345-587], Ptrend &lt;0.01) and an extent of CACt tertiles (265 [99-488], 356 [202-458], and 448 [318-574], Ptrend &lt;0.01).

Conclusions
In patients who underwent elective PCI, higher maxLCBI4mm in the PCI target vessel was associated with both higher CACS in the target vessel and total amount of 3-vessel CACS.
Risk of incident renal cell carcinoma in patients with type 2 diabetes on sodium-glucose co-transporter-2 inhibitor users: a population-based cohort study
Authors: Jong G P , Yang T Y 
Published: November 2023

Abstract

Background and aims
Patients with type 2 diabetes (T2D) are at substantially higher risk for developing renal cell carcinoma (RCC) than the general population. Clinical studies have investigated the effects of sodium-glucose co-transporter-2 inhibitor (SGLT-2I) use on the development of incident RCC in patients with T2D, but the findings are inconsistent. This study aimed to examine the association between SGLT-2I use and incident RCC risk in patients with T2D.

Methods
We conducted a nationwide retrospective cohort study using the Taiwan Health Insurance Review and Assessment Service database (2009–2019). The primary outcome was the risk of incident RCC by estimating hazard ratios (HRs) and 95% confidence intervals (CIs). Therefore, multiple Cox regression modeling was conducted to analyze the association between SGLT-2I use and incident RCC risk in patients with T2D.

Results
In a cohort of 241,772 patients with T2D using SGLT-2I and 483,544 participants not using SGLT-2Is, 220 and 609 incident RCCs were recorded, respectively. There was a decreased risk of incident RCC for SGLT-2I users after adjusting for the index year, sex, age, comorbidities, and concurrent medication (adjusted HR 0.68, 95% CI 0.58–0.81) compared with non-SGLT-2I users. The sensitivity test for the propensity score 1:1-matched analyses showed similar result (adjusted HR 0.67, 95% CI 0.56–0.81).

Conclusions
SGLT-2I therapy may effectively decrease RCC risk in patients with T2D. More studies are needed to credibly evaluate the effects of SGLT-2I therapy on RCC prevention in patients with T2D.
Fifteen-year follow-up and impact of age and sex on cardiovascular outcomes in diabetes and non-diabetes patients without CAD
Authors: Olesen K K W , Thrane P G , Hansen M K , Gyldenkerne C , Maeng M 
Published: November 2023

Abstract

Background
In the absence of angiographically-detectable coronary artery disease (CAD), patients with diabetes have a risk of myocardial infarction that is comparable to patients without diabetes, while still having higher risks of ischemic stroke and all-cause mortality when followed for up to 10 years. In the current study we extended follow-up to 15 years and, additionally, examined the impact of age and sex on cardiovascular risk in diabetes and non-diabetes patients without CAD.

Purpose
To examine the cardiovascular risk and mortality associated with age and sex in diabetes and non-diabetes patients without CAD.

Methods
We included every patient with no or mild CAD when examined by coronary angiography in Western Denmark from 2003-2021 with and without diabetes. We performed age-stratified (&lt;65 year, 65-74 years, and ≥75 years) and sex-stratified analyses. Patients were followed for up to 15 years. Outcomes were myocardial infarction, ischemic stroke, and all-cause death. We estimated adjusted hazard ratios (aHR) using Cox regression.

Results
We included 60,712 patients without angiographically detectable CAD, of whom 7,690 (12.6%) had diabetes. Median age was 62 years and 51% were men. Median follow-up was 9 years ((inter-quartile range 6-13)). Diabetes was associated with an increased 15-year risk of myocardial infarction (5.8% versus 4.1% aHR 1.30, 95% CI 1.13-1.50), ischemic stroke (8.1% vs 4.0%, aHR 1.87, 95% CI 1.66-2.10), and all-cause death (46.2% vs 33.1%, aHR 1.66, 95% CI 1.58-1.73) compared to patients without diabetes. The relative risk associated with diabetes declined by age (Figure 1), while there was no sex-dependent difference associated with diabetes (Figure 2).

Conclusions
At 15-year follow-up, diabetes patients without angiographically-detectable CAD at baseline had a relatively small increased risk of myocardial infarction but a substantial increased risk of ischemic stroke and all-cause mortality. Furthermore, the relative importance of diabetes decreased with age, while being independent of sex. These results support that aggressive multifactorial cardiovascular risk management, even in the absence of CAD and independently of age and sex, should be initiated when diabetes is diagnosed.Figure 1Figure 2
Impact of glycated hemoglobin A1c on cardiovascular risk in diabetes patients with and without coronary artery disease
Authors: Olesen K K W , Thrane P G , Hansen M K , Gyldenkerne C , Maeng M 
Published: November 2023

Abstract

Background
Guidelines recommend a haemoglobin A1c (HbA1c) target &lt;53 mmol/mol (7%) to achieve microvascular risk reduction. However, the impact of HbA1c target levels on macrovascular complications is less certain. Moreover, we have previously shown that the risk of macrovascular complications is dependent on presence of coronary artery disease (CAD).

Purpose
We tested the hypothesis that HbA1c ≥53 mmol/mol is associated with cardiovascular risk in diabetes patients with and without CAD.

Methods
We conducted a contemporary cohort study including diabetes patients examined by coronary angiography in Western Denmark from 2011-2021. The association between HbA1c and major adverse cardiovascular events (MACE, a composite outcome of myocardial infarction, ischemic stroke, and cardiovascular death) was modeled using restricted cubic splines. Patients were followed for up to 10 years. We estimated adjusted hazards ratios (aHR) using HbA1c of 52 mmol/mol as reference. We also performed stratified analyses by presence of CAD.

Results
We included 15,825 patients with diabetes, of whom 12,200 (77%) had CAD. Median HbA1c was 52 mmol/mol in patients with CAD and 51 mmol/mol in patients without CAD. Using restricted cubic splines, we observed significantly increased MACE rates with HbA1c ≥53 mmol in the entire cohort (Figure 1A). MACE rates plateaued with increasing HbA1c above 65 mmol/mol. When stratifying by presence of CAD, this association between HbA1c and MACE was sustained in patients with CAD (Figure 1B). In contrast, we did not observe any relation between HbA1c and MACE rates in patients without CAD (Figure 1C).

Conclusions
The current study suggest two novel findings. Firstly, a HbA1c &lt;53 mmol/mol target is associated with a reduced risk of macrovascular complications in patients with diabetes. Thus, the impact of glucose control on macrovascular complications corresponds to the HbA1c levels recommended for avoidance of microvascular complications. Secondly, the association between HbA1c and MACE is restricted to diabetes patients with CAD while not observed in those without CAD.Figure 1,A-C
Myocardial performance index improves prediction of major adverse cardiovascular events and heart failure in type 1 and type 2 diabetes without known heart disease: Thousand&1 and Thousand&2 study
Authors: Bahrami H , Jorgensen P G , Hove J D , Dixen U , Rossing P , Jensen M T 
Published: November 2023

Abstract

Background
Cardiovascular disease (CVD) is the leading cause of mortality and morbidity in type 1 (T1D) and type 2 diabetes (T2D). Despite myocardial involvement in diabetes, current risk prediction models do not include parameters of the myocardial function. Myocardial performance index (MPI) reflects left ventricular systolic and diastolic function. The prognostic value of MPI has not been evaluated in larger-scale diabetes populations.

Purpose
To assess the prognostic value of MPI in a larger-scale diabetes population.

Methods
We evaluated two prospective cohort studies: The Thousand&1 Study (1093 individuals with T1D) and The Thousand&2 Study (1030 individuals with T2D). Clinical data, including echocardiography, were collected at baseline. We excluded 480 individuals with heart disease. We collected follow-up data from national registries. We defined major adverse cardiovascular events (MACE) as the first incident of all-cause death, hospital admission for acute coronary syndrome, heart failure, or stroke.

Results
For included individuals (56% male, 54±15 years, MPI 0.51±0.1, 63% T1D), follow-up was 100% after a median of 5.3 years (interquartile range: 4.8 to 6.3). MPI was significantly associated with MACE (Hazard ratio 1.2, 95% confidence interval 1.0-1.3, p=0.012, per 0.10-unit increase) and heart failure (Hazard ratio 1.3, 95% confidence interval 1.1-1.6, p=0.005, per 0.10-unit increase) after adjusting for clinical and echocardiographic variables. MPI predicted MACE better in T1D than in T2D (p=0.031 for interaction). MPI added discriminatory power to the Steno T1D Risk Engine (1,2) in predicting heart failure, but not MACE.

Conclusions
MPI is an independent predictor of MACE and heart failure in T1D and T2D, with the strongest prediction in T1D. Echocardiographic assessment in diabetes may enhance risk prediction.
Machine-learning score using CCTA and stress CMR for prediction of cardiovascular events in patients with obstructive CAD
Authors: Pezel T , Garot P , Toupin S , Hovasse T , Hamzi K , Lefevre T , Unterseeh T , Sanguineti F , Neylon A , Ah-Sing T , Goncalves T , Dillinger J G , Henry P , Bousson V , Garot J 
Published: November 2023

Abstract

Background
In patients with suspected or known coronary artery disease, traditional prognostic risk assessment is based on a limited selection of clinical and imaging findings as coronary computed tomography angiography (CCTA) and stress cardiovascular magnetic resonance (CMR). Machine learning (ML) methods can take into account a greater number and complexity of variables.

Purpose
To investigate the feasibility and accuracy of ML using stress CMR and CCTA data to predict major adverse cardiovascular events (MACE) in patients with suspected or known coronary artery disease, and compared its performance with existing clinical, CMR or CCTA scores.

Methods
Between 2008-2020, consecutive symptomatic patients without known CAD referred for CCTA were screened. Patients with obstructive CAD (at least 1 ≥50% stenosis on CCTA) were further referred for stress CMR. Twenty-three clinical, 7 CCTA, and 11 stress CMR parameters were evaluated. ML involved automated feature selection by LASSO, model building with a XGBoost algorithm. The primary composite outcome was MACE defined by cardiovascular death or nonfatal myocardial infarction. The external validation cohort of the ML score was performed in another center (n=274).

Results
Of 2,210 patients who completed CMR, 2,038 (47% male, mean age 69±12 years) completed follow-up (median 6.8 [IQR 5.9-9.2] years); 281 experienced a MACE (13.8%).
The ML score exhibited a higher area under the curve (AUC) compared with ESC risk score, QRISK3 score, Framingham risk score, and CCTA or stress CMR data alone for prediction of MACE (ML score: 0.85 vs ESC score: 0.66, QRISK3 score: 0.64, Framingham score: 0.63, only CCTA score: 0.76, only CMR: 0.82; all p&lt;0.001). Similar results were obtained with AUC of the Precision-Recall (PR) curves (ML score: 0.59 vs. only CCTA score: 0.39, only CMR: 0.45; all p&lt;0.001). The ML score also exhibited a good area under the curve in the external cohort (AUC ROC: 0.85 and AUC PR curve: 0.57).

Conclusions
The ML score including CCTA and stress CMR data exhibited a higher prognostic value to predict MACE compared with traditional method or traditional scores. In addition, our ML score including CCTA and stress CMR data showed the best performance compared with scores using only CCTA or CMR parameters.ROC et PR curves: ML scorePR curves: ML score
Time to act: the challenge of high incidence of diabetes and prediabetes in patients admitted with different cardiovascular diseases phenotypes
Authors: Medovchshikov V , Yeshniyazov N , Khasanova E , Zholdin B , Kurmanalina G , Kobalava Z 
Published: November 2023

Abstract

Background
Limited studies have focused on diagnosing type 2 diabetes mellitus (T2DM) and prediabetes in hospitalized patients with cardiovascular diseases (CVD) with their different phenotypes. In addition, HbA1c levels in patients admitted for cardiovascular reasons may be lower than in patients with symptoms of hyperglycemia.

Purpose
To assess the incidence of newly and previously diagnosed T2DM and prediabetes among patients hospitalized with CVD, depending on the reasons for admission.

Methods
In the single-center prospective study (registry) we enrolled 773 patients ≥40 years with established CVD and arterial hypertension (HTN) without type 1 diabetes mellitus, except for previously diagnosed T2DM and prediabetes who were admitted to the City Clinical hospital. We also assessed the reasons for admission. From 06.01.2018 to 03.01.2020 275 (35.6%) patients hospitalized with acute coronary syndrome (ACS), 163 (21.1%) with acute decompensated heart failure (ADHF), 157 (20.3%) with HTN, 75 (9.7%) with atrial fibrillation or flutter (AF), 67 (8.7%) with chronic coronary syndrome (CCS) and 36 (4.7%) with newly diagnosed T2DM. All of them screened for T2DM and prediabetes using HbA1c and fasting plasma glucose by ADA Guidelines.

Results
Screening results are shown in Picture 1. The overall incidence of T2DM or prediabetes in hospitalized patients with CVD was 55.9%, and before the screening, only 25.7% were diagnosed with T2DM or prediabetes. The highest incidence of T2DM or prediabetes, including previously diagnosed, was among patients admitted with ADHF – 71.2%, and the lowest, 46.2%, in those hospitalized with ACS.
Picture 2 presents mean levels of HbA1c in patients with newly and previously diagnosed T2DM, depending on the reasons for admission. The highest HbA1c levels were identified in patients with CVD who were hospitalized with symptoms of hyperglycemia and in whom the diagnosis of T2DM was confirmed (р&lt;0,001). However, patients hospitalized with ADHF, AF and CCS had a HbA1c level almost twice lower than in patients hospitalized with newly diagnosed T2DM and lower than in those hospitalized with ACS and HTN (р&lt;0,001). At the same time, HbA1c levels in previously diagnosed T2DM did not differ significantly between groups.

Conclusion
Thus, about 1 out of 2 patients hospitalized with CVD have a T2DM or prediabetes, and more than a third of patients without a T2DM or prediabetes (41%) were previously undiagnosed. In addition, patients admitted with ADHF, AF, and CCS with newly diagnosed T2DM had lower levels of baseline HbA1c than patients with overt symptoms of hyperglycemia, ACS, and HTN. All this has a potential impact on the target groups of screening and initial therapy of T2DM, including new classes of drugs.Picture 1Picture 2
Elevated plasma factor XI is predicts cardiovascular complications in patients with type 2 diabetes mellitus
Authors: Paszek E , Polak M , Bryk-Wiazania A , Konieczynska M , Natorska J , Zabczyk M , Undas A 
Published: November 2023

Abstract

Background
Atherothrombotic complications are common in patients with type 2 diabetes mellitus (T2DM), reflecting a chronic prothrombotic state. Circulating factor XI (FXI) has been associated with a prothrombotic fibrin clot phenotype and predicted myocardial infarction, stroke and cardiovascular (CV) death in a number of diseases, including CAD. Its role in T2DM is largely unknown.

Purpose
The purpose of this study was to assess plasma FXI as a predictor of atherothrombotic events in T2DM patients. We also aimed to establish the determinants of elevated plasma FXI in this group of patients.

Methods
In a cohort of 156 patients aged 43–83 years, 56% male, with T2DM of a median duration time of five years, 64.7% with diagnosed CAD, we measured FXI along with a number of fibrin clot parameters, including turbidity, permeation, compaction, lysability, maximum concentration of D-dimer (D-D max), and rate of D-dimer release during tissue plasminogen activator-induced clot lysis. Patients were followed for a median time of 72 (68-74) months for a composite endpoint of nonfatal myocardial infarction (MI), nonfatal stroke, and cardiovascular (CV) death.

Results
Follow-up was complete for 133 (85.3%) patients. There were 21 (16%) cases of the composite endpoint, including one nonfatal MI, four nonfatal strokes and 16 cases of CV death. Patients with and without the composite endpoint shared a similar demographic and clinical profile with the exception of age and white blood cell count – patients with the endpoint were older (69.4 [8.4] vs. 65.4 [7.8] years, p=0.03) and had a higher leukocyte count (7.8 [1.9] vs. 7.0 [1.3], p=0.02) as compared with the remainder. FXI was elevated above the upper limit of 120% in 25 (18.8%) patients, including 16 (61.9%) with the composite endpoint vs. 12 (10.7%) without the composite endpoint, p&lt;0.001. Individuals with the composite endpoint had higher baseline FXI concentrations as compared with the remainder (120.1±16.8 vs. 104.9±10.7%. p &lt; 0.001), along with higher D-D max (4.1 [3.8-4.3] vs. 3.8 [3.6-4.1] mg/l, p = 0.006) and slightly longer lysis time (t50% 10.1 [9.8-10.9] vs. 9.8 [8.9-10.4] min, p = 0.03). On multivariable analysis, co-existing CAD, LDL cholesterol, and thrombin activatable fibrinolysis inhibitor activity were independent predictors of elevated FXI in T2DM patients.

Conclusion
Elevated plasma FXI in T2DM patients is associated with CAD, LDL cholesterol and TAFI, and predicts myocardial infarction, stroke, and CV death in long term follow-up. Our finding may have implications for risk stratification and suggests a role for FXI inhibitors in T2DM patients with a high risk of atherothrombotic complications.