bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of Sleep Apnea and cardiovascular mortality in CAD patients
Authors: Costa L , Scudeler T L , Nunes R A B , Santana G C , Pereira D C G , Brito T M , Oliveira R P 
Published: October 2024

Abstract

Background
A growing body of epidemiological and clinical research has uncovered a significant relationship between sleep apnea and the exacerbation of cardiovascular outcomes, notably myocardial infarction, stroke, and cardiac death. Individuals diagnosed with coronary artery disease (CAD) alongside sleep apnea are identified to have a heightened likelihood of experiencing recurrent cardiovascular events. Despite these associations, the link between sleep apnea and an elevated risk of mortality among CAD patients remains insufficiently explored.

Purpose
Our study aims to shed light on the impact of sleep apnea on mortality rates within this patient population, potentially guiding future therapeutic strategies.

Methods
Our cohort study leveraged data from the TriNetX multinational electronic health record network, focusing on patients aged 18 and above diagnosed with coronary artery disease. Participants were stratified into two groups based on the diagnosis of sleep apnea. To ensure a fair comparison, we adjusted for prevalent risk factors such as hypertension, diabetes, dyslipidemia, obesity, and chronic kidney disease, which are commonly observed in CAD patients.

Results
The study encompassed 1,799,812 patients, equally divided into two groups of 899,906 individuals each, one with sleep apnea and the other without. Over a 5-year observation period, the primary endpoint, defined as event-free survival, was significantly lower in the sleep apnea group (74.385%) compared to the non-sleep apnea group (76.606%), with a Log Rank confidence interval of 1.128 to 1.148 and a p-value of &lt;0.0001. This outcome highlights a association between sleep apnea and increased mortality rates in CAD patients.

Conclusion
The findings from our large cohort study underscore the critical impact of sleep apnea on mortality among patients with coronary artery disease. The diagnosis of sleep apnea in CAD patients within the TriNetX cohort was significantly associated with a higher mortality rate over a span of five years. These insights emphasize the need for integrated care strategies that not only address the primary cardiovascular conditions but also prioritize the diagnosis and management of sleep apnea to potentially improve survival outcomes in this vulnerable patient group. Our study calls for heightened clinical awareness and further research to elucidate the mechanisms behind this association and to explore the benefits of targeted sleep apnea interventions in reducing mortality rates among CAD patients.5-year Kaplan-Meier curves for mortality
Prognostic role of remnant cholesterol and traditional cardiovascular risk factors in young adults: results of long-term follow-up of a cohort of 30-year-old norwegians
Authors: Aaseth E , Halvorsen S , Helseth R , Gravning J 
Published: October 2024

Abstract

Background
There are limited data on the prevalence and impact of traditional cardiovascular (CV) risk factors among young adults. In addition, more knowledge on novel CV risk factors is needed to explain the residual risk beyond that of the traditional risk factors. Increasing evidence suggest a causal role of remnant cholesterol (RC) in the development of atherosclerotic cardiovascular disease (CVD) and subsequent clinical events. However, the role of RC in young adults is unresolved.

Purpose
We aimed to evaluate the prevalence of traditional risk factors and the respective sex-differences in young adults, as well as their association with long-term CV events. Further, we hypothesized that higher RC concentrations are associated with impaired CV prognosis.

Methods
In year 2000, all 30-year-old inhabitants of our city were invited to a cross-sectional study including assessment of health status, anthropometric measurements, and non-fasting blood samples. RC was calculated as total cholesterol minus (LDL-C + HDL-C). Long-term clinical follow-up was performed through linkage with mandatory national registries, 22 years after inclusion. The primary outcome was a composite of cardiovascular death, non-fatal myocardial infarction, non-fatal ischemic stroke, hospitalization for unstable angina and coronary revascularization.

Results
A total of 5950 individuals were included (56% women). At baseline, men displayed significantly higher systolic and diastolic blood pressure, total cholesterol, LDL-C and triglycerides, as compared with women (Table 1). Also, men had higher levels of RC (Table 1). During a mean follow-up time of 22 years, 108 events (1.8%) occurred. In multivariable Cox regression analysis, non-West-European ancestry (adjusted [a] HR 1.76, 95% confidence interval [CI] 1.03-2.99), diabetes mellitus (aHR 6.39, 95% CI 2.52-16.2), systolic blood pressure (aHR 1.03, 95% CI 1.01-1.04), and LDL-cholesterol (aHR 1.37, 95% CI 1.11-1.68) were associated with an increased risk of CV events during long-term follow-up. Female gender was associated with a reduced risk of CV events (aHR 0.38, 95% CI 0.23-0.64), whereas smoking status did not show any significant association. RC was identified as a significant predictor of CV events (aHR 1.55, 95% CI 1.11-2.18, per 1.0 mmol/L increase). The highest RC quartile (mean RC: 1.1 mmol/L), had the highest event rate (Figure 1, p&lt;0.001 with log-rank test).

Conclusion
This study uncovers significant sex-differences in modifiable CV risk factors among young adults at the age of 30, which are associated with increased risk for long-term CV events. Interestingly, increasing concentrations of RC at the age of 30 were strongly associated with impaired long-term CV outcome and should be accounted for in early risk prediction.Baseline characteristics.Remnant cholesterol and CVD events.
External validation of the Systematic COronary Risk Evaluation 2 (SCORE2) model in cancer patients
Authors: Gynnild M N , Holtrop J , Hageman S , Vinje V , Dorresteijn J , Visseren F , Holte E , Dalen H , Wethal T , Omland T 
Published: October 2024

Abstract

Background
Guidelines recommend cardiovascular disease (CVD) risk stratification before cancer treatment to better identify patients for intensified follow-up or cardioprotective treatment. Only a limited number of CVD risk stratification tools exists for cancer patients which at present is not widely used nor extensively validated. The ESC Guidelines on Cardio-oncology 2022 suggest using traditional CVD models like the SCORE2 (Systematic Coronary Risk Estimation 2). However, external validation in cancer populations is lacking.

Purpose
Our aim was to study the prevalence of CVD risk factors and incidence of cardiovascular events in a cancer cohort and externally validate the Systematic COronary Risk Evaluation 2 (SCORE2) model in this context.

Methods
We included 1058 patients from a large-scale populational study without diabetes or established CVD aged 40 to 69 years and diagnosed with cancer between 2006 and 2012. Participants were assessed for cardiovascular risk factors at baseline and followed until Sept 2023. The Norwegian Cancer Registry provided patient specific information about cancer characteristics and therapy. The primary outcome was the combination of myocardial infarction (MI), stroke or CVD mortality, which was retrieved from the local hospitals’ registries and the national causes of death registry. Performance was assessed using smooth calibration curves of predicted and observed risk and Harrel’s C-statistic for discrimination, both corrected for competing risks. SCORE2 was recalibrated by adapting the model with a single multiplicative constant based on the expected-to-observed ratio (E/O-ratio).

Results
The most common cancer types were gastrointestinal cancer (19%), male genital including prostate cancer (19%) and breast cancer (18%). Mean (SD) age was 58.6 (7.6) years, 54% were female. Prevalence of cardiovascular risk factors are shown in Table 1. In total, 121 (11%) individuals had a CVD event (MIs 53 (44%), strokes 46 (38%) and CVD deaths 22 (18%)) during a median (interquartile range) follow-up of 11.1 (3.4 to 13.1) years, and 360 (34%) died due to non-CVD causes. Calibration plots showed adequate agreement between estimated and observed 10-year prognosis after recalibration (C-statistics 0.685, 95% CI 0.643 to 0.728), Figure 1. E/O-ratio for men was 0.65 and for women 0.63, indicating underestimation of the observed CVD incidence. After recalibration, the median estimated 10-year risk was 8.1% (IQR 5 to 11), 36% had &gt;10% 10-year risk and 9% had &gt;15% 10-year risk.

Conclusion
SCORE2 underestimated CVD risk in a general cancer population but showed adequate agreement after recalibration and C-statistics aligned with the original external validation cohorts. SCORE2 is useful also in cardio-oncology setting (after recalibration) to identify individuals at higher risk of developing CVD.
Implications of five different risk models in primary prevention guidelines
Authors: Sud M , Sivaswamy A , Austin P , Abdel-Qadir H , Anderson T , Naimark D , Lee D , Roifman I , Thanassoulis G , Tu K , Wijeysundera H , Ko D 
Published: October 2024

Abstract

Background
A lack of consensus exists across guidelines as to which risk model should be used for the primary prevention of cardiovascular disease (CVD).

Purpose
The objective of this study was to determine potential improvements in the number needed to treat (NNT) with statins using different risk models in patients eligible for risk stratification.

Methods
A retrospective observational cohort was assembled from primary care patients in Ontario, Canada between January 1st, 2010, to December 31st, 2014 and followed for up to 5 years. Risk estimation was undertaken in patients 40-75 years of age, without CVD, diabetes, or chronic kidney disease using the Framingham Risk Score (FRS), Pooled Cohort Equations (PCEs), a recalibrated FRS (R-FRS), Systematic Coronary Risk Evaluation 2 (SCORE2), and the low-risk region recalibrated SCORE2 (LR-SCORE2).

Results
The cohort consisted of 47,399 patients (59% women, mean age 54). The NNT at 5 years with statins was lowest for SCORE2 at 40, followed by LR-SCORE2 at 41, R-FRS at 43, PCEs at 55, and FRS at 65. Models that selected for individuals with a lower NNT recommended statins to fewer, but higher risk patients. For instance, SCORE2 recommended statins to 7.9% of patients (5-year CVD incidence 5.92%). The FRS, however, recommended statins to 34.6% of patients (5-year CVD incidence 4.01%; Figure).

Conclusions
Newer models such as SCORE2 may improve statin allocation to higher risk groups with a lower NNT.Figure
Adding ethnicity to cardiovascular risk prediction: external validation and model updating of SCORE2 using data from the multiethnic HELIUS population cohort
Authors: Van Apeldoorn J A N , Hageman S H J , Harskamp R E , Agyemang C , Van Den Born B J H , Van Dalen J W , Galenkamp H , Richard E , Valkengoed I G M , Visseren F L J , Dorresteijn J A N , Moll Van Charante E P 
Published: October 2024

Abstract

Background
Current prediction models for mainland Europe do not include ethnicity, despite ethnic disparities in cardiovascular disease (CVD) risk.

Purpose
We evaluated the performance of SCORE2 across the largest ethnic groups in the Netherlands with and without the factor of ethnicity.

Methods
We linked data from 11,614 participants enrolled between 2011 and 2015 in the prospective, multi-ethnic HELIUS cohort study, the Netherlands, aged between 40 and 70 years without CVD with hospital data. Variables (age, sex, smoking status, blood pressure, cholesterol) and outcome first CVD event (myocardial infarction, stroke, CVD death) were consistent with SCORE2. We used Fine and Gray models to calculate sub-distribution hazard ratios (SHR) for South-Asian Surinamese, African Surinamese, Ghanaian, Turkish and Moroccan origin groups, relative to the Dutch origin group, on top of individual SCORE2 risk predictions. Model performance was evaluated by discrimination, calibration and net reclassification index (NRI).

Results
Overall, 274 fatal and non-fatal CVD events, and 146 non-cardiovascular deaths were observed during a median of 7.8 years follow-up (IQR 6.8–8.8). SHRs for CVD events were 1.86 (95% CI 1.31-2.65, p=0.0005) for the South-Asian Surinamese, 1.09 (95% CI 0.76-1.56) for the African-Surinamese, 1.48 (95% CI 0.94-2.31) for the Ghanaian, 1.63 (95% CI 1.09-2.44, p=0.018) for the Turkish, and 0.67 (95% CI 0.39-1.18) for the Moroccan origin groups. Adding ethnicity to SCORE2 led to comparable calibration and discrimination [0.76 (0.74-0.79) vs. 0.77 (95% CI 0.74-0.78)]. The NRI for adding ethnicity to SCORE2 was 0.24 (95% CI 0.18-0.31) for events and -0.12 (95% CI -0.13--0.12) for non-events.

Conclusion
Adding ethnic backgrounds improves risk classification of the SCORE2 risk prediction model in a middle-aged, multi-ethnic Dutch population, which may help to address disparities in CVDs through timely treatment.
Enhancing primary prevention: the incremental predictive value of NTproBNP beyond ASCVD risk assessment
Authors: Simoes De Azevedo Massa Pereira J , Andraz S , Hamann L , Alex Costa H , Espirito Santo M , Azevedo P , Carvalho D , Fernandes R , Bento D , Sousa Bispo J , Mimoso J 
Published: October 2024

Abstract

Background
Atherosclerotic cardiovascular disease (ASCVD) is a global health challenge, prompting widespread use of conventional risk assessment tools (SCORE2 in Europe and the ASCVD Risk calculator in the United States) to guide preventive strategies. Emerging evidence indicates that NTproBNP may help refine risk stratification. We investigate whether measuring NTproBNP in primary prevention correlates with mortality and enhances prediction compared to conventional risk score stratification.

Methods
Utilizing National Health and Nutrition Examination Survey (NHANES) data (1999 to 2004) linked to the National Death Index, our cohort included individuals without a history of CVD at baseline and suitable for assessment of the ASCVD ACC/AHA risk score. Individuals were grouped based on computed 10-year risk (low: &lt;5%; borderline: 5-7.5%; intermediate: 7.5-20%; high: ≥ 20%). NTproBNP levels were measured (Roche assay, cut-off &gt; 125pg/mL considered as positive). Cox regression estimated the association between ASCVD risk categories, with or without NTproBNP, and all-cause and cardiovascular mortality.

Results
Among 5257 adults, 47% male, mean age 54 ± 9.1 years, the mean 10-year ASCVD risk was 8.17 ± 8.2%, grouped as: low: 53.3%; borderline: 11.5%; intermediate: 23.9%; and high: 11.3%. NTproBNP &gt; 125pg/mL was measured in 12.2%, 16%, 23.2% and 48.6% individuals, respectively (p &lt; 0.001). Over 16.2 ± 3.4 years, all-cause and cardiovascular death was 22.3% and 5.6%, respectively. Compared to low-risk, the hazard ratio (HR) for all-cause death increased to 2.85 (2.2-3.7), 5.6 (4.2-7.5), and 15.3 (11.7-19.9) for borderline, intermediate, and high-risk, respectively. A significant interaction with NTproBNP was observed (low: HR 1.96 (1.33-2.9); borderline: HR 2.5 (1.6-3.9); intermediate: HR 2 (1.6-2.6), high: HR 1.7 (1.4-2.2), p&lt;0.01 for all interactions, see Fig. 1). For cardiovascular death, a significant interaction also occurred across the groups, but of higher magnitude in low and borderline groups (low: HR 3.2 (1.4-7.3); borderline: HR 5.5 (2.5-12.4), p &lt; 0.001 for both).

Conclusion
Our findings suggest that NTproBNP provides incremental predictive value, approximately doubling the hazard of all-cause death across all risk categories, and more than tripling the hazard of CV death in low/borderline risk groups, compared to ASCVD risk alone. The integration of NTproBNP measurements into risk assessment strategies could refine primary prevention approaches.
Comparison of cardiovascular disease risk assessment tools for heart failure prediction among cancer patients
Authors: Soh C , Marwick T 
Published: October 2024

Abstract

Background
Cancer survivors are at an increased risk of incident heart failure (HF) due to shared risk factors and cancer treatment-related cardiac dysfunction. Clinical assessment of HF risk would be an important first step towards HF prevention in survivors. This study compared HF risk calculators in survivors.

Methods
In this study from the UK Biobank, cancer and HF diagnoses were determined based on the International Classification of Diseases (ICD)-10 code and non-cancer participants were excluded. Participants risk of HF incidence was determined using the ESC Cardio-Oncology Risk Assessment (CORA), the Atherosclerosis Risk in Communities (ARIC-HF), Pooled Cohort Equations to Prevent Heart Failure (PCP-HF) and a general cardiovascular risk score (the Systematic Coronary Risk Evaluation [SCORE2]). The predictive performances of each were compared using the area under the curve (AUC).

Results
Of 43,720 survivors, 9,232 had breast cancer or lymphoma (mean age 60 years, 88% female), and 34,488 had other cancer types (mean age 60 years, 59% female). The discriminative value for CORA (AUC 0.757 [95%CI: 0.747-0.768]) and ARIC-HF (0.748 [95%CI: 0.737-0.758]) were similar, and superior to PCP-HF (0.701 [95%CI: 0.689-0.714]) and SCORE2 (0.685 [95%CI: 0.673-0.697]). The overall performance for each risk score was better among participants in other cancer types than those with breast cancer and lymphoma.

Conclusions
CORA and ARIC-HF outperformed the other scores, although all showed suboptimal discrimination for incident HF. A cancer-specific HF prediction tool could facilitate HF prevention among survivors.
Investigating lifestyle determinants of carotid intima-media thickness: cross-sectional insights from the UK biobank cohort
Authors: Mitra S , Biswas R K , Nova A , Hooijenga P , Cassidy S , Kroeger C M , Fontana L 
Published: October 2024

Abstract

Background/Introduction
Carotid intima-media thickness (CIMT) is recognised as a crucial marker for cardiovascular disease (CVD) risk, inherently associated with vascular ageing and influenced by biomarkers such as elevated levels of HbA1c, dyslipidaemia, and hypertension. The significance of CIMT lies in its potential to act as a surrogate marker for CVD risk, bridging a gap in understanding the progression of vascular health.

Purpose
This study aims to investigate the correlation between CIMT and a composite biomarker score to enhance risk assessment and guide the prevention and treatment strategies for CVD. By examining this relationship, the study seeks to underline the importance of CIMT progression as an indicative marker for cardiovascular health.

Methods
A subset of participants from the UK Biobank, with valid CIMT measurements taken in 2014, was selected for this analysis. CIMT was measured through ultrasound techniques and considered the primary outcome variable, treated as continuous in the analysis. A linear regression model was used to examine the correlation between CIMT and lifestyle risk factors, with a focus on the moderating effects of sex.

Results
The study included 29,292 UK Biobank participants (48% female, mean age 64 years), with a mean CIMT of 687.11µm (SD 124.28). Significant predictors of CIMT were age (β=6.05) and male gender (β=13.02). Lifestyle factors such as body weight (β=0.84) and high physical activity (β=10.66) were positively correlated with CIMT. Current smokers showed a stronger association with CIMT (β=14.47) compared to former smokers (β=9.21). In females, age (β=6.07), body weight (β=0.71), CRBI score (β=9.95), and previous smoking (β=6.64) positively correlated with CIMT, while high CRP levels were negatively associated (β=-0.61). In males, significant factors included age (β=6.04), body weight (β=0.95), CRBI score (β=10.79), and smoking history, with previous smokers showing a stronger effect (β=11.67) and high physical activity notably associated with increased CIMT (β=18.73).

Conclusion(s)
The study's findings highlight the impact of lifestyle choices on vascular health, demonstrating that active living, maintaining a healthy weight, and abstaining from smoking can positively affect CIMT and thereby reduce CVD risk. The results confirm the importance of weight management for arterial health across all demographics and highlight the role of abnormal biomarker levels in increasing CIMT. This study contributes to a deeper understanding of the factors affecting CIMT and, by extension, cardiovascular health, advocating for targeted lifestyle interventions to mitigate CVD risk.
Exploring protein biomarkers of physical activity and cardiovascular disease
Authors: Enarsson M , Gustafsson S , Feldreich T , Lampa E , Sundstrom J , Arnlov J 
Published: October 2024

Abstract

Background
The beneficial effects of physical activity on cardiovascular risk are well documented. Yet, the underlying mechanisms by which physical activity prevents cardiovascular disease remain unclear (1). Advancements of omics technology enables us to explore novel biomarkers of this complex molecular relationship and potentially unravel underlying molecular mechanisms involved in the progression of cardiovascular events.

Purpose
To investigate associations between long term physical activity and plasma proteins. As a second step investigate associations between identified plasma proteins and future myocardial infarction and mortality.

Methods
In the population based prospective cohort Uppsala Longitudinal Study of Adult Men (ULSAM), men were repeatedly investigated with a validated questionnaire on physical activity at ages 50, 60 and 70. 720 plasma proteins were analyzed at age 70 (n=782) with follow up on mortality data for 30 years.
In the case-cohort MIMI (Markers of Imminent Myocardial Infarction study) the same plasma proteins were measured in disease-free individuals from six European cohorts. Individuals with acute myocardial infarction within 6 months from baseline were defined as cases (n=420) and up tto four cohort representatives per case were defined as controls (n=1598).

Results
Higher level of physical activity during 20 years was significantly associated with 12 plasma proteins, in a linear regression model adjusted for age, education and smoking after Bonferroni correction for multiple testing (p&lt;0.000069). After additional adjustment for known cardiovascular risk factors (education, smoking status, BMI, blood pressure, low-density lipoprotein, diabetes diagnosis, and hypertensive-, lipid- or diabetes-treatment), all 12 proteins remained negatively associated with higher level of physical activity in the ULSAM cohort (p&lt;0,05). Two proteins of the 12 proteins associated with physical activity were also significantly associated with future myocardial infarction in the MIMI study (FGF21 and IL6, p&lt;0.05 for both) and 10 proteins were associated with increased mortality risk in the ULSAM cohort (p&lt;0.05 for all). Moreover, proteins that were more negatively associated with physical activity were generally more positively associated with the risk of myocardial infarction in MIMI (Figure).

Conclusion
Multiple novel associations were found between long-term physical activity and plasma proteins. Some proteins were also associated with future myocardial infarction in an independent cohort which could suggest that the cardioprotective effects of physical activity to some degree may be mediated via the circulating proteome. Our findings encourage additional studies in order to understand the underlying causal mechanisms of these associations.