bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of a healthy plant-based heart-protective diet with reduced cardiovascular disease incidence and mortality: findings from the UK Biobank Study
Authors: Wang T , Nova A , Cassidy S , Fazia T , Mitra S , Kroeger C M , Masedunskas A , Bernardinelli L , Willett W C , Fontana L
Published: October 2024

Importance

Previous research examining the effects of omnivorous and plant-based diets on CVD outcomes has produced inconsistent findings, and the importance of diet quality is overlooked.

Objective

To assess the relation between adherence to a healthy plant-based, heart-protective diet and the risk of cardiovascular disease (CVD) events.

Design: Prospective cohort study.

Methods and Results

192,274 (mean age: 56.3±7.9 years, 43.3% males) participants in UK Biobank without CVD at baseline who completed a 24-hour recall questionnaire. Using data generated by Oxford WebQ, we developed a novel heart-protective diet score (HPDS) based on 22 food groups. Cox proportional hazard models were used to study associations. During a median follow-up of 12.3 years, there were 20,692 CVD events and 1,131 CVD deaths. After adjusting for demographics, Townsend deprivation index, lifestyle factors, and history of chronic diseases, participants in the top quartile of the HPDS were at the lower risk of overall CVD (HR: 0.92, 95% CI: 0.88 to 0.95), ischemic heart disease (HR: 0.88 [95% CI: 0.83 to 0.93]), myocardial infarction (HR: 0.82, 95% CI: 0.74 to 0.90), and heart failure (HR: 0.86, 95% CI: 0.78 to 0.95) than those in the bottom quartile. Participants who adhered closely to a healthy plant-based heart-protective diet had the lowest risk of overall CVD (HR: 0.72, 95% CI: 0.61 to 0.86), ischemic heart disease (HR: 0.68, 95% CI: 0.52 to 0.89), myocardial infarction (HR: 0.65, 95% CI: 0.46 to 0.91), and heart failure (HR: 0.51, 95% CI: 0.30 to 0.85) mortality.

Conclusions

and relevance: Adherence to a healthy plant-based heart-protective diet rich in non-starchy vegetables, fruits, whole grains, legumes, and fish, is associated with a reduced cardiovascular disease incidence and mortality. Further research in diverse ethnic populations is necessary to validate our findings and enhance their generalizability.
Cocoa flavanols alleviate early diastolic dysfunction by decreasing left atrial volume in healthy elderly individuals
Authors: Duse D A , Groene M , Ophoff N , Kramser N , Schweers H , Schroeter H , Quast C , Boenner F , Heiss C , Sansone R , Jung C , Kelm M , Erkens R
Published: October 2024

Background

Enlargement of the left atrium (LA) predicts future cardiovascular events. Current guidelines recommend cocoa flavanol (CF) intake as it provides cardiovascular and metabolic benefits, although underlying mechanisms are not fully revealed. In this study, we hypothesized that CF intake reverses LA enlargement as a surrogate marker for diastolic dysfunction in elderly individuals without cardiovascular diseases.

Methods and Results

In a randomized, double-blinded trial, we investigated the effects of CF on systolic and diastolic heart function in healthy elderly individuals. Precise assessment of left-atrial and left-ventricular volume as well as strain rates, all together as emblems of early subclinical cardiac impairment, and markers of systolic function were measured by high-resolution cardiac magnetic resonance (CMR) imaging before and after CF intake. Sixty-three participants (59% male) aged ≥ 55 years received either 500 mg CF (n=30) or a placebo (n=33) twice daily for 30 days. CF counteracted subclinical cardiac dysfunction, evidenced by a reduction in maximal LA volume and LA volume index by 12.6±3.5% (p=0.0063 and p=0.0067) and LV end-diastolic volume (LVEDV) and LVEDV index by ~4.9±1.9% (p=0.049 and p=0.0413). CF intake did not influence strain, strain rate, and systolic function parameters, while the systolic blood pressure decreased by 7 mmHg [~4.7±1.9% (p=0.04)].

Conclusion

We provide evidence that CF intake mitigates early changes of diastolic dysfunction and improves cardiovascular health by reversing left atrial and left ventricular remodeling.

Cocoa flavanol consumption may prevent age-related cardiac changes in healthy elderly individuals and promote a health span free from cardiovascular diseases.
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

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 <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

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<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

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 >10% 10-year risk and 9% had >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

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

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

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: <5%; borderline: 5-7.5%; intermediate: 7.5-20%; high: ≥ 20%). NTproBNP levels were measured (Roche assay, cut-off > 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 > 125pg/mL was measured in 12.2%, 16%, 23.2% and 48.6% individuals, respectively (p < 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<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 < 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

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

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

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<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<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<0.05 for both) and 10 proteins were associated with increased mortality risk in the ULSAM cohort (p<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.
Cystatin C predicts cardiovascular events in patients with coronary artery disease both among patients with and among those without type 2 diabetes
Authors: Plattner T , Larcher B , Mader A , Vonbank A , Leiherer A , Muendlein A , Drexel H , Saely C H
Published: October 2024

Cystatin C is an established biomarker for renal function, and, given the close association of chronic kidney disease and cardiovascular disease might indicate new-onset or deteriorating cardiovascular disease. However, evidence for cystatin C as a predictor of cardiovascular events is limited and controversial. We therefore aimed at investigating the role of cystatin C as a predictor of future cardiovascular events in a high risk-cohort of patients with established coronary artery disease (CAD).

We prospectively recorded cardiovascular events in 1053 patients with angiographically verified CAD over a mean follow-up of 9.5±5.3 years. At baseline, 352 patients had type 2 diabetes mellitus (T2DM) and 701 did not have T2DM.

During follow-up, 560 (53.2%) of our patients suffered cardiovascular events. Cystatin C proved to be a strong and independent predictor for cardiovascular events in the total study cohort (standardized adjusted HR 1.22 [1.12-1.33], p<0.001). When T2DM status was taken into account, cystatin C significantly predicted cardiovascular events both in patients with T2DM (HR 1.18 [1.04-1.35], p=0.011) and in non-diabetic patients (HR 1.23 [1.09-1.38], p<0.001).

We conclude that cystatin C predicts cardiovascular events in CAD patients both among those with and among those without T2DM.
Remnant cholesterol is associated with platelet reactivity for patients with coronary artery disease underwent percutaneous coronary intervention
Authors: Liu M L , Li J W , Yan K L , Yuan J Q , Zhao X Y
Published: October 2024

Background

In recent years, remnant cholesterol has received increasing attention and has been shown to be associated with thrombotic and bleeding events in coronary clinical research, but the mechanisms are not fully understood.

Aim

To investigate the relationship between the remnant cholesterol (RC) and the platelet reactivity in patients with coronary artery disease undergoing percutaneous coronary intervention (PCI) who were receiving the dual antiplatelet therapy (DAPT).

Methods: A total of 10,724 consecutive PCI patients in China from January 2013 to December 2013 were enrolled, among whom 6212 patients had the results of thromborlastogram (TEG) with DAPT for analysis. Low on-treatment platelet reactivity (LTPR) and high on-treatment platelet reactivity (HTPR) were defined as adenosine diphosphate-induced platelet maximum amplitude of TEG<31mm and >47mm, respectively.

Results: A total of 6,212 PCI patients (mean age, 58.24±10.27 years;male, 77.5%) were finally enrolled for analysis. There were 2362 (38.02%) patients in LTPR group, and 1900 (30.59%) patients in HTPR group. For LTPR,when the RC is used as a continuous variable, the multivariate logistic regression showed that RC concentration was independently and negatively associated with LTPR (OR: 0.769, 95%CI 0.610-0.968, p=0.025). For quartiles of RC, the quartile 3 of RC was also associated with LTPR, compared with the lowest quartile (Q1) (OR: 0.854, 95%CI 0.732-0.996, p=0.044). For HTPR, when the RC is used as a continuous variable, the multivariate logistic regression showed that RC concentration was independently and positively associated with HTPR (OR: 1.492, 95%CI 1.162-1.916, p=0.002). For quartiles of RC, compared with the lowest quartile (Q1), the higher quartile of RC (Q2, Q3, Q4) was also associated with HTPR (ORQ2: 1.211, 95%CI 1.024-1.431, p=0.025; ORQ3: 1.380, 95%CI 1.165-1.634, p＜0.001; ORQ4: 1.391, 95%CI 1.143-1.692, p=0.001).

Conclusions: In this large sample real-world study, we firstly reported that the lower RC concentration was an independent risk factor for LTPR, representing a higher risk of bleeding, whereas the higher RC concentration was an independent risk factor for HTPR, representing a higher risk of ischemic. These results suggest that higher or lower RC may increase the potential risk of bleeding or ischemia in patients with PCI, which provides new perspectives on individualized lipid-lowering and antithrombotic treatment strategies for patients with coronary artery disease.
Serum metabolomics improve risk stratification for incident heart failure
Authors: Oexner R R , Ahn H , Theofilatos K , Shah R A , Schmitt R , Chowienczyk P , Zoccarato A , Shah A M
Published: October 2024

Background

The prediction and early detection of heart failure (HF) is vital to reduce its substantial impact on quality of life, survival and healthcare expenditure. Current incident HF risk stratification strategies achieve only modest performance. Moreover, state-of-the-art risk scores focus on commonly acknowledged clinical risk factors, thus necessitating the integration of heterogenous data sources and prioritizing individuals with obvious risk constellations.

Purpose

Here, we explored the predictive value of serum metabolomics (168 metabolites detected by proton nuclear magnetic resonance (1H-NMR) spectroscopy) for incident HF.

Methods

Leveraging data of n = 68,311 individuals and > 0.8 million person-years of follow-up from the UK Biobank (UKB) cohort, we (I) evaluated the association of individual metabolites with incident HF via fitting of per-metabolite COX proportional hazards models and (II) trained and validated elastic net (EN) models to predict incident HF using the serum metabolome. Discriminative performance was benchmarked against a comprehensive, well-validated clinical risk score (Pooled Cohort Equations to Prevent HF, PCP-HF). External validation was conducted in the independent FINRISK study.

Results

Several metabolites were independently associated with incident HF (90/168 adjusting for age and sex, 48/168 adjusting for PCP-HF). Performance-optimized risk models effectively retained key predictors representing highly correlated clusters (≈ 80 % feature reduction). The addition of metabolomics to PCP-HF improved predictive performance (Harrel’s C: 0.768 vs. 0.755, ΔC = 0.013 (95% confidence interval (CI) 0.004 – 0.022), continuous net reclassification improvement (NRI) = 0.287 (95% CI 0.200 – 0.367), relative integrated discrimination improvement (IDI): 17.47 % (95% CI 9.463 - 27.825)). Simplified models only including age, sex and metabolomics performed almost as well as the PCP-HF model (Harrel’s C: 0.745 vs. 0.755, ΔC = 0.010 (95% CI -0.004 - 0.027), continuous NRI: 0.097 (95% CI -0.025 - 0.217), relative IDI: 13.445 % (95% CI -10.608 - 41.454)). Risk and survival stratification was improved by integrating metabolomics. External validation within FINRISK revealed similar patterns using the original model coefficients.

Conclusions

Serum metabolomics improve the prediction of incident HF risk. Scores obtained from the combination of age, sex and metabolomics exhibit similar predictive power as clinical risk models. Offering serum metabolomics to a middle-aged cohort might significantly improve HF risk stratification, thus facilitating preventive efforts. Via a single blood draw, serum metabolomics displays a highly cost- and time-effective, standardizable, and scalable alternative to clinical risk scores involving physical measurements and history taking in addition to clinical chemistry.Relative performance (test split)ROC & DCA plots (test split)
A sex-related analysis on the influence of lipoprotein(a) on primary cardiovascular disease prevention and its interplay with traditional lipid markers: results from a 20-year cohort study
Authors: Giannakopoulou S P , Chrysohoou C , Antonopoulou S , Damigou E , Barkas F , Vlachopoulou E , Dalmyras D , Adamidis P S , Kyrili K , Kravvariti E , Tsioufis C , Pitsavos C , Liberopoulos E , Sfikakis P P , Panagiotakos D
Published: October 2024

Introduction

Elevated lipoprotein(a) [Lp(a)] levels is an established risk factor mediating cardiovascular disease.

Purpose

The relationship between Lp(a) and the first fatal/non-fatal CVD incident over a 20-year period in males and females without CVD was assessed.

Methods

A longitudinal prospective study was conducted during 2002–2022. In 2002, a total of 3,042 CVD-free adults (1,514 males and 1,528 females) were enrolled. A follow-up was carried out after 20 years, in 2022, which included 2,169 participants. Out of these, 1,988 had comprehensive data for the occurrence of CVD. The recommended threshold of 50mg/dL was used to define abnormal Lp(a) status (≥50mg/dL).

Results

During the 2002-2022 period, 718 (i.e. 36%) of participants had a fatal or non-fatal CVD event. Twenty-year CVD-event rate was 35.8% and 40.0% in participants with normal and abnormal Lp(a) levels, respectively. For every mg/dL increase in Lp(a), the odds of having a CVD event within 20 years increases by approximately 0.36% (Hazard ratio (HR) = 1.0036, 95% confidence interval (CI) 1.001,1.007, p=0.048). When stratified by sex the relationship remained significant only in females (HR= 1.006, 95% confidence interval (CI) 1.001,1.011, p=0.023). In the multivariate analysis, significance was lost after adjusting for low- and high-density lipoprotein (LDL-C, HDL-C) and triglycerides (HR= 1.0017, 95% confidence interval (CI) 0.998,1.005, p=0.348).

Conclusion

Elevated Lp(a) levels are linked to higher CVD risk, particularly in females. Despite growing efforts to clarify Lp(a) as a risk-predicting marker in CVD, clinical guidelines still require definitive evidence, particularly from a sex-focused perspective.
False-positive cardiac troponin I values in healthy athletes post COVID-19 Infection: concerning insights from a prospective cohort study
Authors: Kaplan E , Kissel C K , Bernasconi L , Lopez-Ayala P , Wittfooth S , Neyer P , Hure G , Sanzone A , Manka R , Noack P , Hof D , Hammarsten O , Hammerer-Lercher A , Mueller C
Published: October 2024

Background

Cardiac troponin I and T (cTnI, cTnT) are cardiac-specific biomarkers that detect and quantify cardiomyocyte injury. In patients with symptoms possibly indicating acute myocardial infarction (AMI), detection of elevated cTnT or cTnI concentrations usually mandates invasive coronary angiography. Accordingly, false-positive cTnT or cTnI concentrations could have detrimental consequences. Unfortunately, little is known about the prevalence and triggers of false-positive cTnI concentrations. Based on two index cases seen by one of us, we hypothesized that false-positive cTnI values may be common after COVID-19 infection and that macrotroponin, a complex formed between endogenous cTn autoantibodies and circulating cTn, may be the underlying cause.

Purpose

We aimed to test these hypotheses in a prospective cohort study.

Methods

We prospectively investigated professional athletes coming to the mandatory return to sports investigation at least 10 days after COVID-19 infection between 2022 and 2023 in an observational study. The presence of false-positive cTnI was centrally adjudicated in individuals that had elevated cTnI concentrations with one (or two) high-sensitivity cTnI assays, but normal high-sensitivity cardiac troponin T concentrations and normal electrocardiography (ECG), normal echocardiography, and normal cardiac magnetic resonance imaging (CMR). Divergences in hs-cTn concentrations were investigated using sex-specific upper limits of normal (ULN) of 4 different assays (hs-cTnI: Alinity/Abbott Diagnostic, hs-cTnI: Atellica/Siemens Healthineers, hs-cTnI: Access Beckman Coulter; hs-cTnT: Cobas/Roche Diagnostics). Athletes were instructed to cease training 48 hours before blood testing. Athletes with divergent hs-cTn assay results underwent further analysis for macrotroponin using sucrose gradient ultracentrifugation.

Results

Among 35 enrolled athletes (median age 24 years, 19 women and 16 men), 18 athletes had normal hs-cTn concentrations with all four hs-cTnT/I assays. In 17 athletes (48.6%), hs-cTn concentration was increased in at least one assay above the ULN, mostly one hs-cTnI method (hs-cTnI, Alinity) with normal concentrations of the other assays and normal cardiac imaging results. In contrast, two athletes had elevations in all hs-cTnI/T assays. Sucrose gradient ultracentrifugation provided evidence of macrotroponin in 15 of the 17 athletes (88%).

Conclusions

False-positive cTnI values are common after COVID-19 infection and should be considered in the differential diagnosis. Assay interference by macrotroponin seems to be the underlying mechanisms in most individuals. Documentation of normal hs-cTnT concentrations helps in the early detection of false-positive cTnI values.
AI-enabled automated cardiac chambers volumetry in non-contrast ECG-gated cardiac scans vs. non-contrast non-gated lung scans
Authors: Naghavi M , Reeves A P , Atlas K , Zhang C , Budoff M J , Henschke C , Yankelevitz D
Published: October 2024

Introduction

We have developed an AI-enabled automated volume measurement of cardiac chambers (AutoChamber) that works on ECG-gated coronary artery calcium scans and correlates well with contrast enhanced coronary CT angiography scans. We have recently reported that increased left atrial volume measured by AutoChamber is a strong predictor of new onset atrial fibrillation (AF) in asymptomatic individuals of Multi-Ethnic Study of Atherosclerosis (MESA). In this study, we compare the volumetry results in ECG- gated CAC scans with those of non-gated full-chest lung cancer screening scans in the same individuals.

Methods

We have studied 169 cases of paired ECG-gated cardiac CT scans and non-gated lung scans obtained from Harbor UCLA. Mean±SD for age was 62.1±10.0 years with 52% female participants. All cases were asymptomatic and were scanned for preventive health assessment. AutoChamber was run on all cases by an independent operator who was not involved in data analysis. P value was calculated using a two-tailed test of significance with α=0.05.

Results

AutoChamber in cardiac scans vs lung scans reported volume (Mean±SD) for left atrium (LA) was 63.8 ± 18.5 vs. 65.5 ± 19.4, left ventricle (LV) 102.8 ± 25.3 vs. 105.5 ± 25.2, right atrium (RA) 81.9 ± 20.5 vs. 85.7 ± 21.9 right ventricle (RV), 140.7 ± 34.2 vs. 134.2 ± 33.7, left ventricle wall (LVW) 113.0 ± 26.6 vs. 109.7 ± 27.0 respectively (P < 0.0001). Strong correlation was shown between cardiac and lung scans for each cardiac chamber: LA (R = 0.92), LV (R = 0.93), RA (R = 0.91), RV (R = 0.92), and left ventricular wall (LVW) R = 0.95.

Conclusions

AutoChamber volumetry results are similar in ECG-gated cardiac scans vs non-gated full-chest lung scans. This AI-enabled automated tool is promising as it can provide added value to patients undergoing coronary calcium and lung cancer screening scans flagging enlarged cardiac chambers at risk of AF and heart failure.
Opportunistic screening of coronary artery calcification on non-gated conventional CT scans using artificial intelligence
Authors: Aviv Y , Awesat J , Abitbol M , Tamir T , Hermann D , Hudadi N , Shiyovich A , Weissman M , Shafir G , Nachmias K , Mizrahi N , Kimmel Y , Kornowski R , Hamdan A
Published: October 2024

Background

Recent advancements in artificial intelligence (AI) led to the development of automatic Coronary artery calcification (CAC) analysis based on chest CT scans. The objective of this study is to assess the impact of AI-based CAC evaluation on improving the allocation of add-on therapies and further evaluation.

Methods

We used a novel propriety AI software to estimate CAC from non-gated, non-contrast chest CT scans. Patients were categorized into groups: low CAC 0-99 Agatston unit (AU), moderate CAC 100-399AU, and high CAC ≥ 400 AU. Exclusion criteria included prior myocardial infarction, percutaneous coronary intervention (PCI), coronary artery bypass graft (CABG), and life expectancy < 2 years. Patients classified as high CAC were invited to a dedicated clinic to perform a risk factor and clinical assessment, initiate appropriate medication, and refer to further testing as needed. For low-moderate CAC, referring physicians were informed of CAC status, encouraging guideline-based optimal preventive management.

Results

1272 eligible patients between January 1th, 2023 to February 29th, 2024 were evaluated for inclusion. 641/1272 (50.3%) were excluded. Out of 631 enrolled patients, 84 (13%) patients were classified as high CAC, 163 (26%) as moderate and 348 (61%) as low CAC. At the dedicated clinic, appropriate low-density lipoprotein (LDL) goals were assigned and statins were initiated or dose adjusted where necessary. Twenty patients were referred to myocardial perfusion imaging, of which 2 were referred for invasive coronary angiography, one of them underwent PCI (Figure), and the other was referred for CABG.

Conclusion

This ongoing study indicates routine CAC quantification using AI software on chest CT scans can identify patients who may benefit from preventive cardiology services and lead them to appropriate cardiac treatment pathway. Further follow-up is required to assess its clinical impact.
Left ventricular flow dynamics and energetics derived from 4D flow CMR in patients with low gradient severe aortic stenosis
Authors: Wang Y S , Shan Y , Li J , Wu B T , Lu F W , Shu X H , Ge J B
Published: October 2024

Background

Up to 40% of patients with severe aortic stenosis (SAS) determined by current guidelines present with discordant Doppler echocardiography findings and demonstrate divergent prognosis. Differentiation of true SAS who generally benefits from aortic valve intervention among this subset of patients is important albeit challenging for clinical management.

Purpose

Left ventricular (LV) 3-dimentional flow characterization was analyzed to illustrate altered intracardiac hemodynamics in different types of low gradient SAS and to investigate its application for the identification of true SAS in comparison with LV stroke volume index (LVSVI) and transaortic flow rate.

Methods

Four-dimensional flow cardiovascular magnetic resonance (4D flow CMR) was performed in 126 patients with low gradient SAS and 30 age- and gender-matched controls. All patients were categorized into 3 groups according to left ventricular ejection fraction (LVEF) and LVSVI as follows: classical low-flow low-gradient (CLFLG, n=37), paradoxical low-flow low-gradient (PLFLG, n=41), and normal-flow low-gradient (NFLG, n=48). Left ventricular flow was partitioned into 4 components: direct flow, retained inflow, delayed ejection flow, and residual volume. Average kinetic energetic parameters indexed to end-diastolic volume (KEiEDV) throughout the systolic phase were analyzed.

Results

Patients with CLFLG and PLFLG SAS had reduced LV direct flow proportion (CLFLG vs. control: 10±5% vs. 35±5%, P<0.001; PLFLG vs. control: 29±6% vs. 35±5%, P<0.001, Figure 1) and systolic ejection-flow KEiEDV (CLFLG vs. control: median, 5.3μJ/ml vs 8.7μJ/ml, P<0.001; PLFLG vs. control: median, 6.0μJ/ml vs. 8.7μJ/ml) compared with controls. Reduced systolic ejection-flow KEiEDV correlated with decreased LVSVI (R=0.47, P<0.001) and transaortic flow rate (R=0.72, P<0.001). Among 126 patients in the study cohort, 74 (59%) were determined as true SAS according to standardized criteria based on flow-independent parameters and demonstrated elevated systolic ejection-flow KEiEDV than patients with pseudo-SAS (median, 6.5μJ/ml vs 5.6μJ/ml, P<0.001). Systolic ejection-flow KEiEDV≥6.1μJ/ml demonstrated an optimal positive predictive value of 90% for distinguishing true SAS from pseudo-SAS among patients with low gradient SAS (Figure 2).

Conclusion

Alterations in LV flow components and kinetic energy were associated with the presence and type of low gradient SAS. LV systolic outflow energetic markers responsible for aortic valve opening could aid the evaluation of AS severity with Doppler-based parameters.Comparison of LV flow componentsROC analysis for discriminating true SAS