bluuebunny/crossref_metadata_2025_split huggingface dataset:
Educational attainment and cardiovascular outcomes in prostate cancer: observations from 3700 men in 6 countries in the RADICAL PC study
Authors: Guha A , Pinthus J , Valle F , Piccoli R , Dusilek C , Duceppe E , Kann A , Fradet V , Shayegan B , Violette P , Koo C , Beato P , Villareal N , Cavalli G , Leong D 
Published: October 2024

Abstract

Background
Educational attainment has been associated with improved cardiovascular outcomes in individuals with or at high risk for cardiovascular disease (CVD). There is little information on the relationship between education and CVD outcomes in individuals with cancer. Also, we have limited understanding of what mediates the relationship between education and these outcomes.

Purpose
To evaluate the relationship between educational attainment in patients with PC and CVD event (CVE) or all-cause mortality.

Methods
We prospectively studied 3,778 men with PC from 55 sites in 7 countries (median age 69 years), 46% on ADT. Inclusion criteria were one of: PC diagnosed in the past 12 months; started ADT within the past 6 months; or plan to start ADT in the next month. Educational attainment was classified as those who attained primary school education vs. those who attained high school education vs. those who attained greater than high school education. Participants were followed for a median of 2.5 years from enrolment to document CVE: myocardial infarction, angina, stroke, cerebrovascular disease, peripheral arterial disease, arterial revascularization, heart failure, venous thromboembolism, and atrial fibrillation. The primary outcome for this analysis was CVE or death. All outcomes were evaluated by Cox proportional hazards models adjusted sequentially for age, race, physical activity levels, tobacco use, and alcohol use.

Results
Among 3,778 participants, 726 (19%) achieved primary school education, 1,001 (27%) high school, and 2,051 (54%) greater than high school education.
On univariate analysis, as compared with participants with greater than high school education, those with high school education and primary school education had respective HR (95% CI) of 1.33 (1.05-1.69) and 2.19 (1.71-2.83).
Adding age, race, tobacco, and alcohol use to the Cox model progressively attenuated the association between education and the primary outcome. Eventually, after adjustment for these characteristics and physical activity levels, the relationship between education and the primary outcome was no longer significant (Table).

Conclusion
This finding suggests that patterns of tobacco and alcohol use and physical activity, which are modifiable behaviors, account for the relationship between education and death or CVE in patients with prostate cancer.Table
Safety and efficacy of immune checkpoint inhibitors in patients with pre-treatment reduced left ventricular function
Authors: Tzuberi M T , Brzezinski R B , Flint N F , Solemsn M S , Waissengrin B W , Barak R B , Golomb I G , Wolf I W , Topilsky Y T , Banai S B , Kapusta L K , Laufer-Perl M 
Published: October 2024

Abstract

Background
Immune checkpoint inhibitors (ICIs) have revolutionized the clinical outcomes of cancer. Nevertheless, the response varies across populations and their use may lead to ICIs-related adverse events (irAEs), including cardiovascular (CV) irAEs, which can be life-threatening. Limited evidence exists regarding the safety and efficacy of ICIs therapy in patients presenting with pre-treatment reduced left ventricular ejection fraction (LVEF).

Objectives
To evaluate the safety and efficacy of ICIs therapy in patients with pre-treatment reduced LVEF.

Methods
Retrospective single center cohort of patients treated with ICIs therapy, who performed pre-treatment LVEF assessment. The primary endpoint was to evaluate the safety of ICIs among this population, assessed by CV irAEs (composite of myocarditis, acute coronary syndrome, heart failure, and arrhythmia). The secondary endpoint was to evaluate the efficacy of ICIs, assessed by all-cause mortality and progression-free survival (PFS).

Results
The cohort included 307 patients with 30 (10%) patients presenting with pre-treatment reduced LVEF, with a mean LVEF of 39±7%. While a significantly higher prevalence of CV irAEs was observed in the reduced LVEF group (37% vs. 14%, p=0.004), following a multivariable cox regression analysis including baseline cardiovascular diseases and risk factors, pre-treatment reduced LVEF did not remain a significant predictor (p=0.635). No significant differences were observed between the groups regarding all-cause mortality and PFS.

Conclusions
Pre-treatment reduced LVEF was found to be safe with no significant impact on efficacy among patients treated with ICIs.
Understanding the impact of heart failure treatment on cancer growth
Authors: Civati C , Goovaerts B , Van Berlo B , Segers V , De Keulenaer G 
Published: October 2024

Abstract

Background
Heart failure (HF) is associated with systemic alterations that extend beyond the cardiovascular system. The dysregulation of physiological pathways induced by HF, encompassing inflammatory or neurohormonal pathways, may foster an environment conducive to cancer growth and the spead of metastases. It is unknown whether these alterations are attenuated when HF is treated, and whether certain therapies for HF may yield more significant effects than others.

Purpose
This study aims to investigate whether myocardial infarction (MI)-induced left ventricular (LV) dysfunction promotes breast cancer growth and triggers the development of lung metastases. Additionally, it compares the potential impact of different therapeutic strategies for LV dysfunction on cancer development.

Methods
Myocardial infarction (MI) was induced in 11-week-old female BALB/c mice by ligation of the left anterior descending (LAD) coronary artery, leading to LV dysfunction and significant dilation within four weeks. Starting 2 weeks after surgery, mice with ejection fraction (EF) &lt; 40% received daily oral gavage of vehicle or one of three drugs: carvedilol (10 mg/kg), enalapril (20 mg/kg), or empagliflozin (15 mg/kg). Four weeks post-surgery, 2x105 4T1 metastatic breast cancer cells were injected into the 4th mammary fat pad. Tumor volume was measured every two days, starting eight days after injection. Weekly echocardiographic assessments monitored cardiac function until the end of the experiment. Tumors were excised on day 22 after injection. Mice were euthanised on day 28 for post-mortem analysis. MCM2 proliferation staining was performed on lung tissue to quantify metastases.

Results
Among the HF treatments, only empagliflozin (n=11) induced a significant decrease in both left ventricular end-diastolic and end-systolic volume (Fig. 1.A; p=0.0043; Fig. 1.B; p=0.0186) compared to the vehicle group (n=11). Tumor weight and volume (Fig. 1.C-D) were not different in the HF/vehicle group (n=15) and the sham-operated group (n=13). Carvedilol (n=14) led to a small reduction in tumor weight (Fig. 1.C; p=0.1264), while empagliflozin (n=11) exhibited a significant reduction in both tumor weight (Fig. 1.C; p=0.0306) and volume (Fig. 1.D; p=0.0268). In addition, carvedilol (n=13) significantly reduced lung metastases (Fig. 1.E; p=0.0347) compared to the HF/vehicle group (n=13). Enalapril (n=10) and empagliflozin (n=9) did not significantly impact the development of lung metastases.

Conclusion
Despite the absence of increased cancer growth post-MI, our findings indicate that specific treatments for HF—namely, carvedilol and empagliflozin—attenuate cancer growth post-MI. Furthermore, carvedilol demonstrated potential in reducing metastatic spread. Additional research is required to uncover the underlying mechanisms both in the presence and absence of HF, and to explore the molecular impact that HF treatments have on various stages of cancer progression.Figure 1
Machine learning and traditional analysis of the interaction between cardiovascular diseases and hematological malignancies
Authors: Caller T , Fardman A , Sharon E , Naftali-Shani N , Leor J , Maor E , Itkin T 
Published: October 2024

Abstract

Background
Cardiovascular diseases and clonal hematopoiesis of indetermine potential (CHIP), the premalignant state of hematological cancers, exhibit reciprocal interactions. While the presence of CHIP confer a risk for heart failure, it is unclear if cardiovascular diseases are associated with elevated risk hematological cancers.

Purpose
To determine the association between cardiovascular diseases (CVD) and cardiovascular risk, and hematological cancer.

Methods
We evaluated 27,231 adults, free of CVD and cancer, who participated in preventive healthcare program between 2000-2018. Each participant underwent a complete physical evaluation, blood test and exercise stress test at baseline. CVD was defines as ischemic heart disease, stroke, atrial fibrillation or hypertension. Then, we used machine learning and traditional survival analysis to evaluate the association between CVD and hematological cancer. For machine learning, we used the random forest method using Curat package in r, and incorporated all continuous variables gathered into the model (70% training, 30% test). For survival analysis, we first matches each CVD patient to a control patient by propensity scores to balance for age, sex, smoking, diabeles mellitus, renal function, body mass index and length of follow-up. Then, we compared the CVD and non-CVD patients using cox proportional hazard regression.

Results
Using machine learning, we found that the strongest predictors for hematological cancer in our cohort are low eGFR, age, high atherosclerosis cardiovascular disease score (ASCVD) and BMI. Of note, systolic and diastolic blood pressure were also strong predictors of hematological cancer (Figure A). Then, we matched 5500 CVD patients to controls with median follow-up of 9.2 years (Interquartile range 5-15 years). During follow-up, 1380 developed cancer. Of them, 186 developed hematological cancer. We used cox proportional hazard regression and Kaplan Mayer method to determine the risk and hazard ratio of developing hematological cancer (Figure B-C). Compared with subjected without CVD, patients with CVD were 91% more likely to develop cancer during follow-up, and 62% more likely to develop hematological cancer (Figure C, HR=1.61. 95%CI 1.21-2.16). Moreover, the 10-year risk to develop hematological cancer was 1.9% for patients with CVD and 1.0% for individuals without CVD (Figure D). Notably, the increased incidence of hematological cancers included 38% increase in cases of leukemia but only 11% increase in cases of lymphoma.

Conclusions
Using machine learning and traditional analysis we show that CVD risk and CVD were associated with increased incidence of hematological cancer. Understanding this relationship could lead to advances in cardiovascular and cancer treatment and could ultimately help to improve patient outcomes.
Adverse cardiovascular events in patients with cancer: a biomarker-enhanced clinical risk score
Authors: Kraler S , Liberale L , Nopp S , Englisch C , Grilz E , Akhmedov A , Lapikova-Bryhinska T , Carbone F , Suter T M , Von Eckardstein A , Pabinger I , Luescher T F , Montecucco F , Ay C , Moik F 
Published: October 2024

Abstract

Background/Introduction
Continuously improving cancer-specific survival puts a growing proportion of cancer patients at risk of major adverse cardiovascular events (MACE), but reliable tools for cardiovascular risk prediction remain unavailable (1).

Purpose
To assess a broad panel of cardiovascular biomarkers and clinical risk factors and to provide a novel risk score for the prediction of MACE in cancer patients.

Methods
Among 2’192 patients with newly diagnosed or recurrent cancer, a broad panel of cardiovascular biomarkers, including NT-proBNP, P-/E-/L-selectins, ICAM-1, VCAM-1, sLOX-1, CRP, and Lp(a) were measured by blinded study personnel. Patients were followed prospectively for the occurrence of 2-year MACE and 5-year cardiovascular death (2,3). Uni- and multivariable competing risk models were fit to assess independent associations of cardiovascular risk factors and biomarkers with MACE, and a risk score was developed.

Results
Beyond clinical risk factors, ICAM-1, P-/E-/L-selectins and NT-proBNP levels were independently linked to 2-year MACE risk, though shape of associations differed markedly. A clinical risk score was derived, assigning +1 point for male sex, smoking, and age ≥60 years, and +2 points for ASCVD history, yielding a bootstrapped C-statistic of 0.76 (95%CI:0.71-0.81). Implementation of cardiovascular biomarkers conferred improved performance (0.83, 95%CI:0.78-0.88). A simplified model, solely informed by clinical variables and readily available NT-proBNP (+1 point for NT-proBNP≥230pg/mL), achieved similar performance (0.80, 95%CI:0.74-0.86), with a cumulative 2-year MACE incidence of 0% in low- and 11.0% in high-risk patients.

Conclusions
Cancer patients are at substantial MACE risk. The herein presented first-of-its-kind risk score, integrating traditional cardiovascular risk factors and biomarkers, including NT-proBNP, effectively predicts 2-year MACE and 5-year cardiovascular death.
Double product derived from exercise stress echocardiography (ESE) or dobutamine stress echocardiography (DSE) in patients with a history of breast cancer and radiotherapy (RXT) exposure and MACE
Authors: Garzon-Dangond J , Gomez-Ardila M F , Tellez-Garcia E , Daryanani A E , Peethambaram P P , Thicke L A , Stan D L , Villarraga H R 
Published: October 2024

Abstract

Background
Breast cancer survivorship has markedly improved in the last two decades due to improved therapies. Among these, adjuvant chest radiotherapy stands out as an integral part of the current treatment. Chest radiotherapy can trigger accelerated atherosclerosis, which, coupled with cardiovascular (CV) risk factors common to this population, can lead to increased rates of coronary artery disease (CAD). ESC 2022 guidelines have established both Exercise Stress Echocardiography (ESE) and Dobutamine Stress Echocardiography (DSE) as cost-efficient and reliable tools for screening this patient population. Recommendations include ESE or DSE 5 years after radiotherapy as a screening tool. Double product (DP), an index common to both tests, parallels myocardial oxygen consumption. It has been used to predict major adverse cardiovascular events (MACE) in other cohorts.

Purpose
We sought to evaluate if DP could be used as a prognostic indicator for MACE (myocardial infarction, stroke, cardiovascular death, and heart failure) in this population.

Methods
Breast cancer patients treated with adjuvant radiotherapy from 2000 to 2022 were included. ESE or DSE was done after a mean of 5.4 years (1Q-2.2, 3Q-7.5) post-radiotherapy. Uni and multivariable adjusted Cox regression models were performed to evaluate the association between DP quartiles achieved and the risk of MACE in DSE and ESE groups. MACE-free survival among different quartiles was plotted with the Kaplan Meier method.

Results
696 patients were included, with a mean age of 65 (SD 10.0) and 72 (SD 9.4) in ESE and DSE respectively. 61% of patients had ESE. In ESE, we observed increased rates of MACE in the 1st quartile when compared to the other quartiles (Figure 1a). On the other hand, univariate and multivariate Cox models established that for every increase of 1000 units of DP achieved during ESE, there is a risk-reduction of 9% [HR=0.91 (0.86-0.95); p=&lt;0.01] in the future incidence of MACE, thus establishing DP as a protective marker. Additionally, advanced age was shown to be a major risk factor as well [HR=4.58 (1.91-10.9); p=&lt;0.01].
In the DSE cohort however, the development of MACE was equally distributed across DP quartiles even after adjusting for existing comorbidities (Figure 1b). Cox analysis did not establish DP as a prognostic tool in this cohort (Table 1).

Conclusion
DP is established as an excellent prognostic tool for the detection of MACE in patients who underwent ESE. Patients who achieve higher DP quartiles during these tests have lower future rates of MACE. Regarding DSE, DP is not a good prognostic tool. This could be explained by higher burden of cardiovascular risk factors in this patient population. ESE should be recommended when possible.
Can the presence of aortic or coronary artery calcifications in the standard of care baseline CT or PET-CT scan of patients with Hodgkin or non-Hodgkin lymphoma be used as a predictor of MACE?
Authors: Gomez Ardila M , Daryanani A , Garzon-Dangond J M , Tellez-Garcia E , Ricaurte-Carmona C , Cerhan J R , Foley T A , Villarraga H R 
Published: October 2024

Abstract

Background
Major adverse cardiovascular events (MACE), commonly defined as acute myocardial infarction, acute coronary syndrome/ischemic heart disease requiring revascularization, stroke, and heart failure, represent a significant cause of mortality among patients with cancer.  With increased rates of both cancer and cancer survivorship, the identification of new predictive markers for the development of MACE in this population is crucial for implementing effective preventive and risk-mitigation strategies.

Purpose
To determine whether the presence of calcifications in the coronary arteries (CAC) or aorta (CA) of lymphoma patients, as reported in standard-of-care PET-CT (Positron Emission Tomography-Computed Tomography) or chest CT (Computed Tomography) scan, can predict the occurrence of MACE.

Methods
A Retrospective analysis was conducted on a cohort of patients diagnosed with Hodgkin or non-Hodgkin lymphoma and treated with anthracycline-based chemotherapy. Patients were diagnosed from January 1, 2013, and followed through to June 30, 2023. The reference point for the study was the radiologist’s report of the PET-CT or chest CT conducted before the initiation of anthracycline therapy. Patients who did not undergo a PET-CT or CT before the start of treatment, and/or developed MACE before treatment initiation were excluded. Univariate and multivariate adjusted Cox regression models were employed to assess whether the presence of CA and CAC was associated with the development of MACE. Associations with outcomes were evaluated using the Kaplan-Meier method and Cox regression.

Results
326 patients were included with a mean age of 55 years (range: 52-60), predominantly male 201 (61%) and white 314 (96%), CAC was reported in 75 patients (23%) and CA in 18 (6%). In the univariate regression model, a statistically significant association was found between the presence of both CA and CAC with the risk of MACE. CAC showed a stronger association with the development of MACE than CA (HR: 3.7 [1-7.9], p=0.0005 vs HR: 2.9 [1- 8.5], p=0.050). In multivariable analysis CAC emerged as the strongest predictor of MACE (HR: 2.9 [1.3 – 6.4], p=0.01), after accounting for hypertension, diabetes, dyslipidemia, and GFR &lt;60 (Table 1), while the association with CA attenuated (HR: 2.01 [0.7-6.5], p=0.2010) and was no longer significant (Table 2).

Conclusion
CAC in the standard-of-care PET/-CT scans was a predictor of MACE in lymphoma patients treated with anthracyclines, while the association with CA weakened in multivariable analyses and was likely underpowered given the small number of patients with CA. If replicated, this finding warrants closer surveillance of this group of patients and can be considered as a non-invasive cardiovascular risk marker.
New onset of left ventricular dysfunction and diastolic dysfunction are uncommon in patients with her2+ breast cancer after completion of cancer therapy
Authors: Osataphan N , Huang F , Yu C , Nardi Agmon I , Sooriyakanthan M , Abdel-Qadir H , Amir E , Thavendiranathan P 
Published: October 2024

Abstract

Background
Cardiotoxicity from anthracyclines and trastuzumab is common among patients with breast cancer during therapy. However, there are limited data on new onset of cardiotoxicity (systolic or diastolic dysfunction) after completion of therapy. This knowledge has implications to guide long-term follow-up.

Purpose
The aim of this study was to evaluate the incidence of cancer therapy related cardiac systolic dysfunction (CTRCD) and diastolic dysfunction (DD) in women with HER2+ breast cancer after completion of cancer therapy and compare to incidence during cancer therapy.

Methods
We conducted a prospective cohort study of women with HER2+ breast cancer who were treated with sequential anthracycline and trastuzumab therapy, with or without radiation therapy (The EMBRACE-MRI trial, NCT02306538). Comprehensive surveillance echocardiograms were performed at baseline and every 3 months during treatment, early post-trastuzumab, then at years 1, 2, and 3 post trastuzumab completion. CTRCD was defined as a reduction in 3D-left ventricular ejection fraction (LVEF) by ≥ 10% from baseline to &lt; 55%. Diastolic dysfunction was defined as per the American Society of Echocardiography guidelines.

Results
A total of 136 female patients, with a mean age of 51.1 ± 9.2 years were recruited. Among them, 15.4% had hypertension, 3.7% had diabetes mellitus, and 10.3% had dyslipidemia. The mean cumulative doxorubicin equivalent dose was 203.9 ± 12.5 mg/m2, 120 patients received radiation therapy with the mean heart dose of 170.8 ± 75.9 cGy. During cancer treatment, 27 out of 136 patients (19.9%) developed CTRCD. In long-term follow-up, due to death or interruption due to the COVID-19 pandemic, follow-up was available in 128 patients at 1 year, 117 at 2 years and 111 at 3 years. 5 of the 27 patients still had persistent LV dysfunction (3 at 1 year, 1 at 2 year and 1 at 3 year), however, there were no new diagnosis of CTRCD post completion of therapy. Of 129 patients with baseline normal or indeterminate diastolic function, new DD was identified in 25/129 patients (19.4%) during cancer treatment (17 grade I, 2 grade II, 6 unable to grade). After completion of cancer therapy, 5 patients had persistent DD. In patients with no DD during therapy and completed 3 year follow-up, 5 patients developed new DD after therapy (2 grade I, 3 unable to grade). Figure 1 illustrates the percentage of patients with new CTRCD or new diastolic dysfunction at each timepoint. None of the patients developed clinical heart failure.

Conclusion
Although both CTRCD and diastolic dysfunction are common during sequential therapy with anthracyclines and trastuzumab in women with HER2+ breast cancer, new onset after treatment completion is rare during a careful follow-up. These findings have implications for long-term surveillance.