Cardiovascular Disease In Cancer Patients Research Articles

Cardio-oncology: a cardiologist's view on the problem of endovascular treatment of patients with coronary artery disease and severe aortic valve stenosis combined with cancer: a literature review

Cardio-oncology is a new medical direction which is responsible for the prevention of development, diagnosis and treatment of cardiovascular disease (CVD) in patients with cancer. The prevalence of cardiac pathology in cancer patients turned out to be unexpectedly high, while only half of the patients with pathology of two systems are referred to a cardiologist for consultation and receive optimal therapy. The coincidence of risk fa­ctors for CVD and cancer suggests that these diseases have common underlying biological and molecular mechanisms. Antitumor therapy and radiation therapy can also contribute to the onset and progression of CVD. Diagnosis of coronary artery disease (CAD) in patients with cancer is difficult, since this group of patients often lacks typical angina pain, and the most common complaint is dyspnea. Endovascular surgery for CAD and severe aortic valve stenosis can be an effective and safe method for treating patients with concomitant cancer. However, given the heterogeneity of cancer diseases and the fact that these patients were not included in most randomized trials studying the CVD treatment, further research is required in this area.Aim. To analyze the literature on the etiopathogenesis of CVD in cancer patients, as well as the clinical features of CAD and aortic valve stenosis in cancer patients and the potential of innovative endovascular technologies.Conclusion. For management and treatment of such severe comorbid patients, the participation of a multidisciplinary team and a personalized approach to each patient are necessary.

Chinese expert consensus on cardiac biomarkers for monitoring and management of cardiovascular toxicity in cancer therapy (2024 edition)

In recent years, the treatment of malignant tumors has continually advanced, significantly extending the survival period of cancer patients. Tumors are increasingly present as chronic diseases over the long term, and the cardiovascular toxicity associated with cancer treatment has become increasingly prominent, severely affecting the effective treatment and survival of cancer patients. As a result, cardio-oncology has gained considerable attention as an emerging discipline. However, cardiovascular diseases in cancer patients often have an insidious onset, and early identification and treatment are frequently overlooked. Throughout the course of cancer treatment, it is crucial to reasonably apply cardiac biomarkers for risk stratification, early identification, and screening of cardiovascular diseases in patients, as well as to improve the early diagnosis and treatment levels of cardiovascular diseases in cancer patients. To this end, Cardio-Oncology Group, Chinese Society of Cardiology in conjunction with Cardiovascular Expert Committee, China Medical Doctor Association of Laboratory Medicine, organized experts in relevant fields to compile this consensus. It aims to provide a basis for clinicians to standardize the screening and management of cardiovascular toxicity related to cancer treatment through the reasonable application of cardiac biomarkers.

Metabolic syndrome and cardiovascular disease among adult cancer patients: results from NHANES 2007–2018

BackgroundMetabolic syndrome (MetS) is a risk factor for cardiovascular disease (CVD), and CVD is a major challenge for cancer patients. This study aimed to investigate the prevalence and association of MetS and CVD among adult cancer patients.MethodsThis cross-sectional study included cancer patients aged > 18 years from the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2018. The prevalence of MetS and CVD was calculated using weighted analysis. Multivariable logistic regression was used to assess the association between MetS and CVD.ResultsThe study included 2658 adult cancer patients, of whom 1260 exhibited MetS and 636 had CVD. The weighted prevalence of MetS and CVD in cancer patients was 45.44%, and 19.23%, respectively. Multivariable logistic regression showed a 79% increased risk in higher CVD prevalence in cancer patients with MetS, with the OR (95% CI) of 1.79 (1.31, 2.44). Notably, obesity, elevated blood pressure (BP), high glucose, and low high density lipoprotein cholesterol (HDL-C) in the MetS components were significantly associated with higher CVD prevalence after adjusting for covariates. Moreover, the risk of CVD prevalence in cancer patients increased with more MetS components. Notably, MetS was more strongly linked to CVD in patients aged < 65 and women.ConclusionsAmong adult cancer patients, over two-fifths (45.44%) were estimated to have MetS, while about one-fifth (19.23%) were considered to have CVD. Notably, obesity, elevated BP, high glucose, low HDL-C, and higher number of MetS components were found to be significantly associated with higher CVD prevalence among cancer adults. Cancer patients under 65 and women with MetS may be at increased risk of CVD.

Arterial Stiffness Changes in Adult Cancer Patients Receiving Anticancer Chemotherapy: A Real-World Bicentric Experience.

Background Chemotherapy correlates to acute and long-term cardiotoxicity, is reflected clinically by myocardial and vascular endothelial dysfunction, and can cause cardiovascular complications. Thus, early diagnosis of cardiovascular disease in cancer patients undergoing anti-cancer treatment is necessary to enhance long-term survival. Our principal objective in this study was to discern the impact of specific anti-cancer chemotherapeutics and biologics on arterial stiffness alterations before and after the administration. Methods Conducted at Mustafa Bacha University Hospital, Algeria, the study focused on arterial stiffness in anti-cancer chemotherapy patients. Assessments included blood pressure, diabetes, and dyslipidemia, with precise measurements using validated systems, particularly pulse wave velocity (PWV). Various chemotherapy protocols were applied, and statistical analysis with R software (R Foundation for Statistical Computing, Vienna, Austria) maintained a significance level of p=0.05. Key outcomes centered on carotid-femoral PWV and secondary endpoints such as central and peripheral pressures and pulse pressure (PP). Univariate and bivariate analyses were conducted using appropriate statistical tests. Results A comparative prospective observational study was completed on 58 patients (34 women and 24 men; mean age: 52.64 +/- 12.12 years) treated with anti-cancer chemotherapy agents. Our evaluation included a complete clinical exam, electrocardiogram, Doppler echocardiography, and applanation tonometry with arterial stiffness measurement using PWV. Patients presented significantly higher levels of carotid-femoral PWV, regardless of the chosen chemotherapy protocol, with no return to the initial level after one year of stopping treatment (p-value < 0.01). Moreover, this increase was more significant in patients with diabetes and hypertension and patients treated with monoclonal antibodies or intercalants. Conclusion This prospective study shows that chemotherapy patients have elevated arterial stiffness, emphasizing the need to assess PWV and monitor cardiovascular risk factors. PP measurement with PWV could improve risk management.

Association of Life's Essential 8 with incident atherosclerotic cardiovascular disease in cancer patients: the Kailuan prospective cohort study.

Association of Life's Essential 8 with incident atherosclerotic cardiovascular disease in cancer patients: the Kailuan prospective cohort study.

Cardiovascular toxicity of tyrosine kinase inhibitors during cancer treatment: Potential involvement of TRPM7.

Receptor tyrosine kinases (RTKs) are a class of membrane spanning cell-surface receptors that transmit extracellular signals through the membrane to trigger diverse intracellular signaling through tyrosine kinases (TKs), and play important role in cancer development. Therapeutic approaches targeting RTKs such as vascular endothelial growth factor receptor (VEGFR), epidermal growth factor receptor (EGFR), and platelet-derived growth factor receptor (PDGFR), and TKs, such as c-Src, ABL, JAK, are widely used to treat human cancers. Despite favorable benefits in cancer treatment that prolong survival, these tyrosine kinase inhibitors (TKIs) and monoclonal antibodies targeting RTKs are also accompanied by adverse effects, including cardiovascular toxicity. Mechanisms underlying TKI-induced cardiovascular toxicity remain unclear. The transient receptor potential melastatin-subfamily member 7 (TRPM7) is a ubiquitously expressed chanzyme consisting of a membrane-based ion channel and intracellular α-kinase. TRPM7 is a cation channel that regulates transmembrane Mg2+ and Ca2+ and is involved in a variety of (patho)physiological processes in the cardiovascular system, contributing to hypertension, cardiac fibrosis, inflammation, and atrial arrhythmias. Of importance, we and others demonstrated significant cross-talk between TRPM7, RTKs, and TK signaling in different cell types including vascular smooth muscle cells (VSMCs), which might be a link between TKIs and their cardiovascular effects. In this review, we summarize the implications of RTK inhibitors (RTKIs) and TKIs in cardiovascular toxicities during anti-cancer treatment, with a focus on the potential role of TRPM7/Mg2+ as a mediator of RTKI/TKI-induced cardiovascular toxicity. We also describe the important role of TRPM7 in cancer development and cardiovascular diseases, and the interaction between TRPM7 and RTKs, providing insights for possible mechanisms underlying cardiovascular disease in cancer patients treated with RTKI/TKIs.

Association of Chronic Kidney Disease with Cardiovascular Disease in Cancer Patients: A Cross-Sectional Study

Introduction: Due to the cardiotoxicity of cancer treatment and traditional risk factors for cardiovascular disease (CVD) such as obesity, diabetes, dyslipidemia, and hypertension, cancer patients are at higher risk of developing CVD. However, limited research exists on the correlation between chronic kidney disease (CKD) and CVD risk in cancer patients. Methods: This cross-sectional study selected cancer patients aged ≥20 years from the National Health and Nutrition Examination Survey (NHANES) conducted from 2015 to 2020. Multivariable logistic regression was used to assess the association between CKD and CVD in cancer patients. Additionally, subgroup analyses were conducted to investigate the association among different groups of cancer patients. Results: We included 1,700 adult cancer patients (52.53% were females). After multivariable adjustment for covariates including traditional CVD factors, CKD was significantly associated with CVD, with an odds ratio (95% confidence interval) and p value of 1.61 (1.18, 2.19) and 0.004. Subgroup analyses after multivariable adjustment showed a significant correlation between CKD and increased CVD risk in the following cancer patients: age ≥60 years, males, white ethnicity, and individuals with or without traditional CVD factors (obesity, diabetes, dyslipidemia, and hypertension). Conclusions: CKD remains a significant factor in the higher risk of CVD among adult cancer patients in the United States, even after adjustment for traditional CVD risk factors. Therefore, to reduce the risk of CVD in cancer patients, it is important to treat CKD as a non-traditional risk factor for CVD and actively manage it.

Risk of cardiovascular diseases in cancer patients: A nationwide representative cohort study in Taiwan

BackgroundThe associations with cancer and cardiovascular diseases (CVD) had inconsistent results. The study aimed to investigate the risk of cardiovascular diseases (CVD) between populations with and without cancer.MethodsPatients with common cancers in Taiwan were enrolled in the study between 2007 and 2018 using the Taiwan Cancer Registry. We focused on colorectal cancer, women’s breast cancer, lung cancer, liver cancer, oral cancer, prostate cancer, and thyroid cancers. The study endpoint was fatal and non-fatal CVD, which was defined as ischemic heart disease and ischemic stroke according to the National Health Insurance Research Database. We compared the risk of CVD between patients with cancer and age- and sex-matched (1:1 ratio) participants who did not have cancer or CVD. Multivariable adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were obtained from Cox regression analysis. To evaluate the chronological trend, we estimated the HRs and 95% CI yearly since the diagnosis.ResultsAmong the 552,485 cancer patients (mean age, 60.6 years; women, 47.7%) during the median follow-up period of 4.1 years, 32,634 cases of fatal and non-fatal CVD were identified. Compared with that noted in the non-cancer population, the overall fully adjusted HR with 95% CI was 1.28 (1.25, 1.30) in the cancer population. The CVD risk was the highest in the first year, the adjusted HR with 95% CI was 2.31 (2.23, 2.40), and this risk decreased yearly.ConclusionsPatients with cancer had a significantly higher risk of fatal or non-fatal CVD. The risk was the highest in the first year since diagnosis and decreased yearly.

Abstract 10825: Tumor-Bearing Induces Cardiomyopathy by Disrupting Cardiometabolic Reprogramming

Introduction: Advances in cancer therapies have significantly improved patient survival. However, prolonged tumor-bearing (TB) survival makes the originally hidden cardiovascular disease become an increasingly important cause of death in tumor patients. In addition, some commonly used chemotherapeutic agents, such as the doxorubicin (DOX), have definite cardiotoxicity. Moreover, epidemiological studies found higher risks of cardiovascular disease in cancer patients than in the general population. This study aimed to investigate the if the TB state leads to cardio-fragility and myocardial sensitivity which further causes excessive cardiotoxicity of DOX in tumor patients. Methods and Results: We established mouse TB models with six types of transplantation tumors. We administrated them and littermate controls with DOX intraperitoneal injections of 10mg/kg weekly for four weeks. The results showed more severer myocardial injury in TB mice than control group based on the echocardiography, cardiac fibrosis, and etc. The RNA-seq, extracellular flux analysis, and PET-CT indicated an increased proportion of myocardial glycolytic metabolism in the TB state. Furthermore, the Secretomic results of clinical cancer patients and control group, along with the Co-IP of TB mice, showed that the TB state induced hyper-phosphorylation of protein tyrosine residues in cardiomyocytes (CMs) via the increase of secreted growth factors, which introduced an elevated expression of pyruvate kinase muscle 2 (PKM2) and increased the proportion of dimer conformation. Meanwhile, those changes allowing re-entry of CMs into the cell cycle and further increased DNA damage co-localization with EdU, eventually led to excessive cardiotoxicity in the TB state by DOX. Finally, treatment with AG-1478 or TEPP-46 with DOX restricted the cardiotoxicity in the TB state, which meanwhile enhanced the tumor-suppressive effect in lung cancer and melanoma models. Conclusion: Our study reveals that differences in tyrosine phosphorylation of CMs between TB and normal states could cause metabolic pattern shift and cell cycle re-entry in CMs. The increased cardio-fragility induced by TB state may be involved in the enhanced cardiotoxic side effects of chemotherapeutics.

DNA damage response signaling: A common link between cancer and cardiovascular diseases.

DNA damage response (DDR) signaling ensures genomic and proteomic homeostasis to maintain a healthy genome. Dysregulation either in the form of down- or upregulation in the DDR pathways correlates with various pathophysiological states, including cancer and cardiovascular diseases (CVDs). Impaired DDR is studied as a signature mechanism for cancer; however, it also plays a role in ischemia-reperfusion injury (IRI), inflammation, cardiovascular function, and aging, demonstrating a complex and intriguing relationship between cancer and pathophysiology of CVDs. Accordingly, there are increasing number of reports indicating higher incidences of CVDs in cancer patients. In the present review, we thoroughly discuss (1) different DDR pathways, (2) the functional cross talk among different DDR mechanisms, (3) the role of DDR in cancer, (4) the commonalities and differences of DDR between cancer and CVDs, (5) the role of DDR in pathophysiology of CVDs, (6) interventional strategies for targeting genomic instability in CVDs, and (7) future perspective.

Analysis of Epidemiological Characteristics of New Cardiovascular Diseases in Cancer Patients with Cardiovascular Disease.

In cancer patients, a cardiovascular disease (CVD) is a prevalent occurrence. When a patient has both heart disease and cancer, the treatment can be complicated because treatment for one condition can have an adverse effect on the outcome of the other. A cardiovascular disease that involves heart failures, coronary artery disease (CAD), stroke, pericardial diseases, arrhythmias, and valve and vascular dysfunction is a serious worry for long-term cancer patients. Because preclinical research is limited, it is critical to comprehend the pathophysiology of CVD as a consequence of anticancerous therapies while taking into account the developing and expanding heart. As a result, in this research, we look at the epidemiological characteristics of cancer patients who also have cardiovascular illness. Low-dose chest computed tomography, cardiac CT, and cardiac magnetic resonance imaging (MRI) are used to acquire the data and perform the screening. Chemotherapeutic drugs such as anthracyclines and trastuzumab are used to treat the condition. Univariate analysis is used to examine risk factors and predict cardiovascular damage. Sensitivity, specificity, positive predictive value, negative predictive value, life expectancy, left ventricular ejection fraction (LVEF), and longitudinal strain are among the metrics examined.

Management and treatment of cardiotoxicity due to anticancer drugs: 10 questions and answers.

Since the introduction of anthracyclines into clinical practice in the 1960s, chemotherapy has always been associated with cardiotoxicity. Patients on cardiotoxic drugs can develop a wide range of cardiovascular diseases, including left ventricular (LV) systolic dysfunction and heart failure (HF), arrhythmias, hypertension, and coronary artery disease (CAD). The rising number of cancer patients, population ageing, and the frequent overlap of cardiovascular and oncological diseases have highlighted the importance of close collaboration between cardiologists and oncologists. As a result, in 1995, cardiologists at the IEO (European Institute of Oncology) coined the term cardioncology, a new discipline focused on the dynamics of cardiovascular disease in cancer patients. Given the complex scenario characterized by a constant dialogue between the oncological condition and cardiovascular comorbidity, it is essential for the clinician to get the knowledge to properly fulfill the needs of the oncological patient under cardiotoxic treatment. Through the answer to 10 questions, we aim to describe the complex issue of cardiotoxicity by addressing the main critical points and current evidence related to the assessment, management, treatment, and surveillance of cancer patients under chemotherapy.

Clonal hematopoiesis and cardiovascular disease in cancer patients and survivors

Cancer genomes have long been known to carry a high number of somatic mutations distributed across many genes. However, recent sequencing studies have unveiled that non-cancerous cells also carry a considerable number of somatic mutations, which are acquired continuously through the lifespan. Accordingly, the pathophysiological relevance of somatic mutagenesis beyond cancer has become a topic of intensive research. Human genetic studies and experiments in mice have shown that some somatic mutations in the hematopoietic system provide a competitive advantage to the mutant cell and allow its clonal expansion. This phenomenon, termed clonal hematopoiesis, is typically driven by mutations in known oncogenes and tumor suppressor genes, and it is associated with a higher risk of hematological malignancies. Unexpectedly, accumulating genetic and experimental evidence strongly suggest that clonal hematopoiesis, at least when driven by certain mutations, also contributes causally to the development of cardiovascular disease and, therefore, represents a new cardiovascular risk factor. While clonal hematopoiesis is relatively common in healthy individuals, especially among the elderly, it is particularly frequent in cancer patients and survivors. Hence, it has emerged as a candidate contributor to the increased risk of cardiovascular complications in cancer patients. This review summarizes our current understanding of the connection between clonal hematopoiesis and cardiovascular disease, with a special focus on the available evidence linking clonal hematopoiesis to cardiovascular disorders that are frequent in cancer patients and survivors.

Cardio-oncology Training in the COVID-19 Era.

Opinion StatementCardio-oncology is a field dedicated to the prevention, diagnosis, and management of cardiovascular disease in cancer patients before, during, and after cancer therapy. It is an emerging field with limited opportunities for structured education and training. In the year 2021, we cannot define the requirements of cardio-oncology training without acknowledging the impact of the global coronavirus disease 19 (COVID-19) pandemic. While this pandemic poses significant health risks to patients with cancer and cardiovascular disease as well as the providers who care for them, it also allows novel opportunities for the nascent field of cardio-oncology to readily adapt. In this article, we detail how the COVID-19 pandemic has impacted all aspects of cardio-oncology training, how programs and trainees can adapt to these challenges, and how lessons learned from the COVID-19 era can continue to positively impact cardio-oncology training for the foreseeable future.

Molecules and Mechanisms to Overcome Oxidative Stress Inducing Cardiovascular Disease in Cancer Patients

Reactive oxygen species (ROS) are molecules involved in signal transduction pathways with both beneficial and detrimental effects on human cells. ROS are generated by many cellular processes including mitochondrial respiration, metabolism and enzymatic activities. In physiological conditions, ROS levels are well-balanced by antioxidative detoxification systems. In contrast, in pathological conditions such as cardiovascular, neurological and cancer diseases, ROS production exceeds the antioxidative detoxification capacity of cells, leading to cellular damages and death. In this review, we will first describe the biology and mechanisms of ROS mediated oxidative stress in cardiovascular disease. Second, we will review the role of oxidative stress mediated by oncological treatments in inducing cardiovascular disease. Lastly, we will discuss the strategies that potentially counteract the oxidative stress in order to fight the onset and progression of cardiovascular disease, including that induced by oncological treatments.

Trends in the Prevalence of Cancer in Cardiovascular Diseases: A Single Center Retrospective Study, 2011-2018.

Recent progress of cancer therapy has increased the number of cancer survivors, in whom cardiovascular diseases (CVDs) have become a big concern. This study aimed to clarify the prevalence of various types of CVDs in cancer patients, using the database of the Cardiovascular Medicine in Kurume University Hospital. This retrospective cohort study enrolled 11,093 hospitalized patients in Cardiovascular Medicine, Kurume University Hospital from April 2011 to March 2019. Among 11,093 enrolled patients, there were 992 CVDs patients with cancer (8.94%). The five most prevalent forms of cancer were colon cancer, prostate cancer, hepatocellular carcinoma, lung cancer, and gastric cancer. Although there was no statistical significance, the comorbidity of breast cancer gradually increased during the study period (2011-2018). In all CVDs, prostate cancer, lung cancer, and uterine cancer tended to increase as comorbidities, while hepatocellular carcinoma and tongue cancer tended to decrease during the observational period. The absolute number of patients with cancer increased in all CVDs, including coronary artery diseases, heart failure, arrhythmia, and pulmonary hypertension. The present study demonstrates that the prevalence of cancer in hospitalized CVDs patients was around 10%, and is showing a tendency to increase. Thus, cancer may have substantial impacts on CVDs treatment.

Abstract 14594: Association Between Life's Simple 7 and Cardiovascular Disease in Cancer Patients Compared to Noncancer Controls in the Aric Cohort

Introduction: Cancer survivors have greater cardiovascular disease (CVD) risk through unclear mechanisms. Little is known about whether Life’s Simple 7 (LS7) metrics differ between persons with and without cancer and if the link between LS7 and CVD is similar in cancer survivors compared to persons without prior cancer. Hypothesis: Persons who develop cancer have poorer LS7 metrics compared to noncancer controls, and an ideal LS7 score is less protective against CVD events in persons with versus those without prior cancer. Methods: A total of 2950 ARIC participants who developed cancer were matched at the time of cancer diagnosis (incidence density sampling) on age, sex, race, and study center, to 5900 noncancer controls. We compared LS7 metrics in individuals who developed cancer (assessed prior to cancer diagnosis) and in matched controls. We used Cox regression to evaluate the prospective association between LS7 score and CVD events (coronary heart disease, heart failure or stroke) stratified by cancer status, with test for interaction between LS7 and cancer. Results: Compared to matched noncancer controls, those who developed cancer were less likely to have an ideal smoking history, body mass index, glucose control, physical activity levels, and diet (defined by LS7 metrics; Table ). Overall those with cancer were less likely to have an ideal LS7 score than noncancer controls (18 vs 23% p&lt;0.0001). Compared to inadequate, an ideal LS7 score was similarly associated with lower CVD risk in persons with and without cancer (HRs 0.37 [95% CI: 0.26-0.52] and 0.40 [95% CI: 0.32-0.50], respectively), with no interaction between LS7 score and cancer status (p = 0.59). Conclusions: Individuals who develop cancer have poorer overall cardiovascular health as reflected by the LS7 score, but an ideal LS7 score is associated with similar cardio-protection in those with and without cancer. Cancer survivors may benefit from interventions targeting cardiovascular health metrics.

Abstract 12653: The Therapy-related Clonal Hematopoiesis Driver Gene Ppm1d Promotes Inflammation and Non-ischemic Heart Failure in a Murine Model

Background: Therapy-related clonal hematopoiesis in cancer patients is typically associated with somatic mutations in hematopoietic cell genes that encode regulators of the DNA-damage response (DDR) pathway. The Protein Phosphatase Mg2+/Mn2+ Dependent 1D ( PPM1D ) gene is the most frequently mutated DDR gene associated with therapy-related clonal hematopoiesis. While epidemiological evidence suggests an association between therapy-related clonal hematopoiesis and cardiovascular disease in cancer patients, causal and mechanistic relationships have never been evaluated in an experimental system. Methods: To test whether hematopoietic cell mutations in PPM1D can increase the susceptibility to cardiac stress, we evaluated cardiac dysfunction in response to angiotensin II infusion in a mouse model where clonal-hematopoiesis-associated mutations in Ppm1d were produced by CRISPR-Cas9 technology. Results: Mice transplanted with hematopoietic stem cells containing clinically relevant mutations in exon 6 of Ppm1d exhibited augmented cardiac remodeling following the continuous infusion of angiotensin II. Ppm1d -mutated macrophages showed impairments in the DDR pathway and had an augmented proinflammatory profile. Mice transplanted with Ppm1d mutated cells exhibited elevated IL-1β in the stressed myocardium, and bone marrow derived macrophages produced more IL-1β in response to LPS stimulation. The administration of an NLRP3 inflammasome inhibitor to mice reversed the cardiac phenotype induced by the Ppm1d -mutated hematopoietic stem cells under conditions of Angiotensin II-induced stress. Conclusions: A mouse model of Ppm1d -mediated clonal hematopoiesis was more susceptible to cardiac stress following of angiotensin II infusion. Mechanistically, disruption of the DDR pathway led to elevations in inflammatory cytokine production, and the NLRP3 inflammasome was shown to be essential for this augmented cardiac stress response. These data indicate that therapy-related clonal hematopoiesis involving mutations in PPM1D could contribute to the cardiac dysfunction observed in cancer survivors.

Role of serum biomarkers in cancer patients receiving cardiotoxic cancer therapies: a position statement from the Cardio-Oncology Study Group of the Heart Failure Association and the Cardio-Oncology Council of the European Society of Cardiology.

Serum biomarkers are an important tool in the baseline risk assessment and diagnosis of cardiovascular disease in cancer patients receiving cardiotoxic cancer treatments. Increases in cardiac biomarkers including cardiac troponin and natriuretic peptides can be used to guide initiation of cardioprotective treatments for cancer patients during treatment and to monitor the response to cardioprotective treatments, and they also offer prognostic value. This position statement examines the role of cardiac biomarkers in the management of cancer patients. The Cardio-Oncology Study Group of the Heart Failure Association (HFA) of the European Society of Cardiology (ESC) in collaboration with the Cardio-Oncology Council of the ESC have evaluated the current evidence for the role of cardiovascular biomarkers in cancer patients before, during and after cardiotoxic cancer therapies. The characteristics of the main two biomarkers troponin and natriuretic peptides are discussed, the link to the mechanisms of cardiovascular toxicity, and the evidence for their clinical use in surveillance during and after anthracycline chemotherapy, trastuzumab and HER2-targeted therapies, vascular endothelial growth factor inhibitors, proteasome inhibitors, immune checkpoint inhibitors, cyclophosphamide and radiotherapy. Novel surveillance clinical pathways integrating cardiac biomarkers for cancer patients receiving anthracycline chemotherapy or trastuzumab biomarkers are presented and future direction in cardio-oncology biomarker research is discussed.

Effects of multidose simvastatin co-administration on pharmacokinetic profile of apatinib in rats by UPLC-MS/MS

Apatinib, a small molecule anti-angiogenic tyrosine kinase inhibitor is used extensively to treat advanced gastric cancer and simvastatin (SV) is often co-prescribed to treat cardiovascular disease in cancer patients. As both apatinib and SV are metabolized primarily by cytochrome P450 variant CYP3A4, they are likely to interact. Therefore, the potential effect of SV co-administration on pharmacokinetics of apatinib in Sprague-Dawley male rats is demonstrated for the first time.Sixteen rats were randomly divided into two groups (n = 8), 2 mg/kg SV orally co-administrated for seven days (group B) and the corresponding control group (group A). Apatinib concentrations of rat plasma samples were detected by ultra-performance liquid chromatography tandem mass spectrometry. Pharmacokinetic parameters were calculated using non compartmental methods.Co-administration of SV for seven days significantly increased area under curve (AUC(0-t)), AUC(0-∞) and maximum plasma concentration of apatinib by 2.4-, 2.4-, and 2.7-fold, respectively while decreasing apparent volume of distribution and clearance by 81.7 and 73.9%, respectively.These findings suggest that concomitant administration of SV with 7 days may have inhibited the metabolism of apatinib in rats.