bluuebunny/crossref_metadata_2025_split huggingface dataset:
Associations of smoking status with long-term cardiovascular events in different arterial territories: the EPIC Norfolk prospective population cohort
Authors: Van Den Bogaart M , Snaterse M , Van Trier T J , Martens F M A C , Boekholdt S M , Jorstad H T 
Published: October 2024

Abstract

Background
Smoking cessation is associated with a reduced risk of cardiovascular disease (CVD) events, mainly in ischemic heart disease (IHD) and stroke. However, the impact of smoking status (never, former or current smoking) on long-term CVD events across different arterial territories remains understudied. Knowledge of such associations is important, as it may assist in risk communication and smoking cessation motivation. We therefore investigated associations between smoking status and territory-specific CVD events in a large cohort with ≥20 years follow-up.

Methods
We included participants without baseline CVD from the European Prospective Investigation of Cancer (EPIC) Norfolk prospective population cohort. The strengths of associations between smoking, former smoking and never smoking with the first occurrence of a CVD event were evaluated using a competing risk-adjusted regression model. CVD events were defined as hospitalisation or death due to IHD, ischemic stroke, haemorrhagic stroke, peripheral arterial disease (PAD) or aortic aneurysm (AA). Patients were followed-up until the first event, non-CVD death (competing risk) or end of study (15-03-2018). The model was adjusted for sex, age, systolic blood pressure, low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c), diabetes, renal function and body mass index. We compared former and current smoking (at baseline) with never smoking.

Results
We included 23,581 participants (56% women) with a median baseline age of 58 years [interquartile range (IQR) 51-66]. During median follow up of 21.3 years (IQR 19.0-22.8), 26.4% experienced ≥1 CVD event. The first event of occurrence was IHD in 17.3%, ischemic stroke in 3.6%, haemorrhagic stroke in 1.4%, PAD in 3.1% and AA in 1.4%. Current (vs. never) smoking was associated with IHD [adjusted hazard rate (aHR) 1.53, 95% confidence interval (CI) 1.36-1.72], PAD (aHR 1.29, 95%CI 1.07-1.56) and AA (aHR 4.81, 95%CI 3.54-6.54). Current smoking was not significantly associated with ischemic stroke (aHR 1.20, 95% CI 0.95-1.52) and haemorrhagic stroke (aHR 1.18, 95% CI 0.81-1.70). In former (vs. never) smoking individuals, the association with AA remained statistically significant but less pronounced [aHR 1.69, 95%CI 1.29-2.23]. Conversely, former smoking was not associated with IHD (aHR 1.07, 95%CI 0.99-1.16) or PAD (aHR 1.09, 95%CI 0.95-1.26) (Figure 1).

Conclusion
After 20-years of follow-up, former smokers, compared to never-smokers, remain at considerably higher risk for CVD events, particularly for aortic aneurysm. This knowledge may assist in treatment decisions and risk communication.
Mean body mass index during 20 years of follow-up and cardiovascular disease incidence: results from the ATTICA cohort study (2002-2022)
Authors: Damigou E , Chrysohoou C , Barkas F , Vlachopoulou E , Vafia C , Dalmyras D , Anastasiou G , Koutsogianni A D , Mentzantonakis G , Kravvariti E , Tsioufis C , Pitsavos C , Liberopoulos E , Sfikakis P P , Panagiotakos D B 
Published: October 2024

Abstract

Background/Introduction
The Global Burden of Disease study has estimated that the burden of increased body mass index (BMI) (i.e., approximately &gt;2.000.000 deaths and &gt;70.000.000 disability-adjusted life years) was predominantly dominated by cardiovascular disease (CVD) during 1990–2017. However, the lifelong body weight (BW) status and its relation to CVD risk remains poorly elucidated.

Purpose
The purpose of this study was to evaluate the relationship between mean BMI during a 20-year period and CVD incidence.

Methods
Participants initially free-of-CVD from the ATTICA cohort study were used (n=1,348). At baseline and the 10- and 20-year follow-up, CVD events were assessed, according to WHO-ICD-10. Based on three measurements of weight and height, BMI for each measurement was calculated, and, afterwards, the mean BMI during the whole 20-year period was computed.

Results
During the whole 20-year period, 41% (n=552) of participants consistently had a normal BW, 48% (n=651) had overweight and 11% (n=145) had obesity. The 20-year CVD incidence was: 8.0% (n=44), 14.9% (n=97) and 19.3% (n=28) in those who consistently had a normal BW, overweight and obesity, respectively (p-value&lt;0.001). In multi-adjusted Cox proportional hazards models, adjusted for age, sex, clinical and lifestyle characteristics, compared to participants who consistently had a normal BW, those who had overweight as well as those who had obesity had almost 2 times higher risk to develop CVD during the 20-year period [Hazard Ratio-HR: 1.73, 95%Confidence Interval-CI: 1.13-2.66 and HR: 2.04, 95%CI: 1.11-3.76, for participants with overweight and obesity, respectively].

Conclusion
The study findings highlight that, despite the observations of the J-shaped relationship between BMI and all-cause mortality observed in some studies, both overweight and obesity can be significant risk factors for CVD, when lifelong BW status is assessed. Therefore, currently, new lifelong measures are needed to prevent and manage the pervasive overweight and obesity.
The visceral adiposity index predicts cardiovascular events both in coronary artery disease patients with and in those without diabetes
Authors: Plattner T , Larcher B , Mader A , Vonbank A , Leiherer A , Muendlein A , Drexel H , Saely C H 
Published: October 2024

Abstract
The Visceral Adiposity Index (VAI) is calculated based on waist circumference, BMI, triglyceride and HDL-cholesterol levels and is a validated measure of visceral adiposity. In the general population, the VAI has been shown to be an independent risk factor for premature mortality. Its power to predict cardiovascular events in patients with coronary artery disease (CAD) with or without type 2 diabetes mellitus (T2DM) is not known and is addressed in the present study.
We prospectively investigated 927 patients with angiographically diagnosed CAD over a mean follow-up time of 8.2±4.3 years.
At baseline, the VAI was significantly higher in patients with T2DM (n=303) than in those who did not have diabetes (6.5±5.2 vs. 4.8±4.9; p&lt;0.001). During follow-up, we recorded 385 cardiovascular events. The VAI significantly predicted the incidence of cardiovascular events both univariately (standardized HR 1.09 [1.02-1.16]; p=0.011) and after adjustment for age, gender, smoking, LDL cholesterol, hypertension and T2DM (standardized adjusted HR 1.11 [1.04- 1.18]; p=0.002); T2DM also significantly predicted cardiovascular events in this fully adjusted model (adjusted HR 1.26 [1.04-1.52]; p=0.018) independently from the VAI.
We conclude that the VAI and T2DM are mutually independent predictors of cardiovascular events in patients with CAD.
Impact of glucose metabolism status on the relationship between remnant cholesterol and ischemic risk after percutaneous coronary intervention: a large-scale long-term cohort study from real-world
Authors: Yan K , Li J , Zhang K , Li Y , Yuan J , Zhao X 
Published: October 2024

Abstract

Background
Elevated remnant cholesterol (RC) is considered a risk factor for ischemic events in patients with coronary artery disease (CAD). Recently evidence demonstrates a close connection between RC and cardiometabolic disorders, particularly diabetes mellitus (DM). However, it remains unclear whether different glucose metabolism statuses modify the association between RC and ischemic risk after percutaneous coronary intervention (PCI).

Purpose
This study aims to explore whether glucose metabolism statuses alter the relationship between RC and ischemic risk in CAD patients undergoing PCI.

Methods
This prospective study enrolled consecutive 10,724 CAD patients undergoing PCI throughout 2013. Patients were categorized into three groups: DM, pre-DM, and normal glucose regulation (NGR) group. Fasting RC was calculated as total cholesterol minus low-density lipoprotein cholesterol and high-density lipoprotein cholesterol, and was analyzed based on tertile levels (low, middle, and high). The clinical endpoint was major adverse cardiovascular and cerebrovascular events (MACCE, including cardiac mortality, revascularization and stroke).

Results
A total of 9,406 PCI patients were ultimately included, among whom the average age was 58.44 ± 10.26 years and 2,142 (22.80%) were female. During 5-year follow-up, 1,876 (19.9%) patients experienced MACCE. In the overall cohort, the highest RC tertile was associated with a higher risk of MACCE (hazard ratio [HR]: 1.129, 95% confidence interval [CI]: 1.006-1.267) compared to those in the lowest tertile (Figure 1). Importantly, a significant interaction was observed between RC levels and glucose metabolism statuses (P for interaction = 0.032). In the DM group, multivariate Cox regression analysis revealed that the highest tertile of RC significantly increased a 1.172-fold risk of MACCE (HR:1.172, 95% CI:1.004-1.369). However, neither the pre-DM nor NGR groups showed any significant association between RC and MACCE (both P &gt; 0.05). Further subgroup analysis found that the correlation between the highest tertile of RC and an increased MACCE risk was only in the DM group, which was prominent among females (Figure 2).

Conclusions
In a large-scale 5-year follow-up study, we are the first to demonstrate that RC-related ischemic risk may be exacerbated by diabetes in CAD patients undergoing PCI, highlighting the potential benefits of intensifying RC-lowering treatments for PCI patients combined with DM.
Interleukin-6 and suPAR improves prediction of all-cause mortality in type 1 diabetes - the Thousand & 1 Study
Authors: Bahrami H , Jorgensen P G , Hove J D , Dixen U , Rasmussen L J H , Eugen-Olsen J , Rossing P , Jensen M T 
Published: October 2024

Abstract

Background
Cardiovascular diseases (CVD) are the leading cause of mortality in type 1 diabetes (T1D). Inflammation frequently accompanies T1D and is suggested as an important contributor to the pathogenesis and progression of CVD. However, current risk prediction models for T1D lack biomarkers of inflammation.

Methods
A prospective study of individuals with T1D without overt heart disease was evaluated. Interleukin-6 (IL-6), soluble urokinase-type plasminogen activator receptor (suPAR) and high-sensitivity C-reactive protein (hsCRP) were analysed. In Cox proportional hazards model, adjustments were made for variables in the Steno T1 Risk Engine: age, sex, duration of diabetes, HbA1c, systolic blood pressure, glomerular filtration rate, albuminuria status, use of statins, tobacco use and physical activity. The model included the biomarkers as continuous variables, and a "combination" category was defined as simultaneously elevated suPAR &gt; 4 ng/mL and IL-6 &gt; 3 pg/mL. The net reclassification improvement (NRI) and C-statistics were calculated.

Results
For included individuals (n=1,014, 52% male, mean age 50±15), follow-up was 100% after median of 12.2 years (interquartile range: 11.8 to 12.9).In the fully adjusted model, IL-6 and suPAR were both associated with all-cause mortality (IL-6 hazard ratio (HR): 1.6 (95% confidence interval: 1.04 to 2.4), suPAR HR: 1.9 (1.2 to 2.9). HsCRP was not associated with the outcome. The combination category showed even stronger association: HR 2.7 (1.4 to 5.1). When added to the Steno T1 Risk Engine, IL-6, suPAR, and their combination all added discriminatory power in predicting all-cause mortality assessed by NRI; IL-6: 38% (19 to 58), suPAR: 45% (25 to 65), combination 56% (36 to 76). C-statistics showed similar results for only suPAR. Area under the curve for suPAR: from 0.84 to 0.86 (P=0.049), IL-6: 0.84 to 0.85 (P=0.338), combination: 0.84 to 0.86 (P=0.066).

Conclusions
IL-6 and suPAR are independently associated with all-cause mortality in T1D without known heart disease. Assessment of IL-6 and suPAR in T1D may enhance risk prediction.Figure 1Figure 2
Effects of glucagon-like peptide-1 receptor agonists, sodium-glucose cotransporter-2 inhibitors and their combination on mitochondrial-derived peptide-c and on markers of neurohumoral activation
Authors: Ikonomidis I , Pavlidis G , Pliouta L , Katogiannis K , Maratou E , Thymis J , Michalopoulou E , Prentza V , Katsanaki E , Vlachomitros D , Kountouri A , Korakas E , Parissis J , Andreadou I , Lambadiari V 
Published: October 2024

Abstract

Background/Introduction
Type-2 diabetes mellitus (T2DM) is associated with increased prevalence of cardiovascular disease.

Purpose
We investigated the effects of insulin, glucagon like peptide-1 receptor agonists (GLP-1RA), sodium-glucose cotransporter-2 inhibitors (SGLT-2i) and their combination on mitochondrial-derived peptide-c (MOTS-c), N-terminal pro B-type natriuretic peptide (NT-proBNP), growth differentiation factor (GDF)-15, oxidant and antioxidant biomarkers and cardiovascular function of T2DM patients.

Methods
A total of 160 T2DM patients were randomized to insulin (n = 40), liraglutide (n = 40), empagliflozin (n = 40) or their combination (GLP-1RA+SGLT-2i) (n = 40) as add-on to metformin. We measured at baseline, at 4 and at 12 months of treatment: a) plasma levels of MOTS-c, NT-proBNP and GDF-15, b) thiobarbituric acid reactive substances (TBARS), as an oxidant biomarkers, and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), as an antioxidant biomarker, and c) global left ventricular longitudinal strain (GLS) and global work index (GWI) using speckle-tracking imaging.

Results
Twelve months after treatment, treatment with SGLT-2i and GLP-1RA+SGLT-2i improved MOTS-c (14.89 ± 11.27 vs. 7.26 ± 4.21 ng/mL, p=0.009, 6.49 ± 3.91 vs. 5.6 ± 3.38 ng/mL, p=0.029, respectively), while treatment with insulin and GLP-1RA had a neutral effect on this biomarker (p &gt; 0.05; Table). GLP-1RA, SGLT-2i and their combination showed a greater reduction of NT-proBNP (-43.1% vs. -54.2% vs. -56.9% vs. -14.7%; Figure) and GDF-15 (-14.8% vs. -15.2% vs. -16.1% vs. -0.9%) than insulin (p &lt; 0.05 for all comparisons), despite the fact that all patient achieved adequate glycemic control. GLP-1RA or GLP-1RA+SGLT-2i provided a remarkable reduction of TBARS and increase of GLS and GWI compared to insulin or SGLT-2i (p &lt; 0.05). In all patients, at 4 and at 12 months, the percentage reduction of NT-proBNP was associated with the improvement of TBARS, GLS and GWI (p &lt; 0.05). The percentage reduction of GDF-15 was correlated with the increase of ABTS and with the improvement of GLS at 4 and 12 months (p &lt; 0.05). In SGLT-2i group, the percentage increase of MOTS-c was related with the percentage reduction of GDF-15 (r = 0.81, p = 0.005) at 12 months.

Conclusions
Twelve-month treatment with GLP-1RA, SGLT-2i and their combination resulted in reduction of cardiac biomarkers in parallel with a greater decrease of oxidative stress than insulin in T2DM. SGLT-2i appears more effective in the improvement of MOTS-c and markers of neurohumoral activation.TableFigure
Association of visceral adipose tissue with echocardiographic abnormalities in type 2 diabetes patients
Authors: Martinez-Dominguez P , Guerra E C , Gomez-Aviles P , Antonio-Villa N E , Almeda-Valdes P , Espinola-Zavaleta N , Santa Ana-Bayona M J , Martagon Rosado A , Campos-Munoz A 
Published: October 2024

Abstract

Introduction
Ectopic deposition of adipose tissue, particularly visceral adipose tissue (VAT) has been identified as a significant contributor to cardiometabolic complications among individuals with type 2 diabetes (T2D). An increase in VAT has been suggested to cause cardiac dysfunction, which may lead to echocardiographic abnormalities such as alterations in speckle-tracking and left ventricular ejection fraction (LVEF). However, this relationship has not been fully elucidated.

Purpose
This study aims to determine the association between VAT and echocardiographic abnormalities in patients with T2D.

Methods
A cross-sectional study in a tertiary hospital which included 195 individuals with T2D, the diagnosis of autoimmune diabetes was excluded. VAT was measured using electrical bioimpedance (BIA), and cardiac function was determined using echocardiography. A Spearman rank correlation analysis was conducted to evaluate the association between VAT and echocardiographic parameters, with significance set at p &lt; 0.05.

Results
Within our cohort, the median age was 57 years, with 37% men. Based on the third quartile (P75) cutoff (5 liters for men, 3.75 liters for women), the population was categorized into P1-75 and P75-100 (Table). There were significant differences in LVEF (61% in P1-75 vs. 58% in P75-100, p = 0.041), left ventricular global longitudinal strain (LV GLS) (P1-75: -20.3%, P75-100: -19.2%, p = 0.012), and conduit phase of left atrial strain (LAScd) (P1-75: 25%, P75-100: 20%, p = 0.046). Positive correlations (Figure) were observed between VAT and indexed LV mass (r = 0.171, p = 0.020), basal diameter of the right ventricle (r = 0.308, p = 0.001), and LV GLS (r = 0.197, p = 0.006). Additionally, negative correlations were observed between VAT and LVEF (r = -0.342, p = &lt;0.001) and right ventricular fractional area change (r = - 0.227, p= 0.001).

Conclusion
Increased VAT was associated with cardiac dysfunction, as indicated by altered LV GLS and LAScd. This study underscores the relevance of VAT in influencing both functional and structural changes in the left and right ventricles. It also highlights the significance of monitoring VAT for comprehensive cardiovascular risk assessment in T2D patients.Clinical demographics tableScatter plots with correlation graphs
Social differences in subclinical coronary artery atherosclerosis in Sweden
Authors: Rosengren A , Andell P , Djekic D , Nilsson P , Soderberg S , Oldgren J , Ostgren C J 
Published: October 2024

Abstract
Most data indicate an inverse relation between socioeconomic status and clinically manifest coronary heart disease that is only partly explained by modifiable cardiovascular risk factors. Few population-based studies have investigated social factors with respect to differences in subclinical coronary atherosclerosis in a healthy population without prior manifest coronary disease.

Purpose
To examine socioeconomic differences in imaging-detected coronary atherosclerosis, and to which extent potential differences could be explained by modifiable risk factors.

Methods
The Swedish CArdioPulmonary bioImage Study (SCAPIS) randomly invited individuals aged 50 to 64 years from the general population. Out of 30,154 participants, we defined a population of healthy participants without prior myocardial infarction or coronary procedures, with technically satisfactory results from coronary computed tomography angiography (CCTA) and coronary artery calcification scoring (CACs). CCTA outcomes were recorded as 1. any coronary atherosclerosis, 2. coronary stenosis ≥50%, 3. segment involvement score (SIS) ≥4, and 4. coronary artery calcium score (CACs) ≥100.

Results
Among 24,616 participants (49.2% women, mean age 57.4 (SD 4.2) years), those with ≤9 compared to ≥12 years of education were heavier, with mean (SD) BMI 28.0 (4.5) compared to 26.1 (4.0) kg/m2, with more hypertension (23.3% vs 15.0%), and diabetes (9.6% vs 4.6%), and with more active smokers (17.4% vs 3.8%). The prevalence of plaque/significant stenosis is shown in the Figure. Findings with respect to low vs high education and odds ratios (ORs) adjusted for age and sex were: 48.8% vs 35.3% for any coronary atherosclerosis, OR 1.31; 95%CI 1.19-14.4; 6.8% vs 4.4% for coronary stenosis ≥50%, OR 1.21; 95%CI 0.99-1.47; 15.7% vs 9.8% for SIS≥4, OR 1.21; 95% CI 0.99-1.47; and 10.1% vs 7.1% for CACS≥100, 1.29; 95%CI 1.12-1.48 (Table). However, after adjustment for coronary risk factors no significant associations with subclinical coronary atherosclerosis persisted.

Conclusions
After adjustment for conventional modifiable risk factors there was no convincing evidence of any independent association between low education and subclinical coronary atherosclerosis. Further studies are needed to explore which other mechanisms could potentially explain an independent link between low socioeconomic status and clinically manifest coronary heart disease.Figure
Low chronotropic response in post-myocardial infarction exercise test predicts worse prognosis in patients with preserved or mildly reduced left ventricular ejection fraction
Authors: Smarz K , Tysarowski M , Ziolo J , Zaborska B , Jaxa-Chamiec T , Budaj A 
Published: October 2024

Abstract

Background
Chronotropic incompetence is common in post-myocardial infarction (MI) patients and is associated with reduced exercise capacity. However, its prognostic significance and a determination of threshold values for prognosis remain unclear.

Methods & Results
We assessed 96 post-MI patients 4 weeks after their initial event with left ventricular ejection fraction (LVEF) ≥ 40%. All patients underwent combined stress echocardiography and cardiopulmonary exercise tests. The chronotropic response was measured as a percent of the maximal predicted heart rate at peak exercise (%MPHR). Exclusion criteria included patients with exercise limitations for pulmonary or peripheral reasons and those who declined to complete the study. Follow-up was conducted in 86 patients. The primary outcome measured was a composite of all-cause mortality or hospitalization for ischemic heart disease events (acute MI, unstable angina, or revascularization procedures) or heart failure exacerbation. The median follow-up duration was 4.0 (IQR 2, 5.6) years. The median patient age was 60 (IQR 53, 65) years, 64% of patients were males, and 84% were on beta-blockers. Median LVEF was 57 (IQR 51, 62)%, and median peak VO2 was 19 (IQR 15, 22) mL/kg/min. There were 15 composite end-point events, including 3 deaths, during the follow-up period. The %MPHR threshold of 67% had the best predictive value with an area under the curve (AUC) of 77% for predicting the primary outcome (PPV 31%, NPV 97%, sensitivity 93%, specificity 55%). A significant difference (p = 0.0022) in the occurrence of the composite end-point was noted between patients with a %MPHR below versus above this threshold (Figure. Kaplan-Meier curves for survival free of primary outcome). In the multivariate Cox regression analysis adjusting for demographic, clinical variables, and beta-blocker doses, only chronotropic response and current smoking correlated with the primary end-point (Table. The Cox proportional hazards regression model for prediction of the primary outcome).

Conclusions
A low chronotropic response to exercise is a negative prognostic marker in post-myocardial infarction patients with either preserved or mildly reduced left ventricular ejection fraction.Figure.Table.