Updates on Anticancer Therapy-Mediated Vascular Toxicity and New Horizons in Therapeutic Strategies

Wang

Front. Cardiovasc. Med.

et al. 2022

PurposeWe aimed to investigate the mortality patterns and quantitatively assess the risks of cardiovascular death (CVD) in patients with colorectal cancer (CRC). We also established a competing-risk model to predict the probability of CVD for patients with CRC.Patients and MethodsPatients with CRC who diagnosed between 2007 and 2015 in the Surveillance, Epidemiology, and End Results (SEER) database were included in the present study. The cumulative incidence function (CIF) was used for CVD and other causes of death, and Gray’s test was used to determine the subgroup difference in CIF. The Fine-Gray proportional subdistribution hazards model was used for identifying independent risk factors for CVD. A novel competing-risk model was established to evaluate the probability of CVD for patients with CRC. The performance of the nomogram was measured by concordance index (C-index), calibration curve, decision curve analysis (DCA), and risk stratification.ResultsAfter a median follow-up of 37.00 months, 79,455 deaths occurred, of whom 56,185 (70.71%) succumbed to CRC and 23,270 (29.29%) patients died due to non-CRC, among which CVD accounted for 9,702 (41.69%), being the major cause of non-cancer deaths. The 1-, 3-, and 5-year cumulative rates for CVD were 12.20, 24.25, and 30.51%, respectively. In multivariate analysis, age, race, marital status, tumor size, tumor stage, advanced stage, surgery, and chemotherapy were independent risk factors of CVD among patients with CRC. The nomogram was well calibrated and had good discriminative ability, with a c-index of 0.719 (95% CI, 0.738–0.742) in the training cohort and 0.719 (95% CI, 0.622–0.668) in the validation cohort. DCA demonstrated that nomogram produced more benefit within wide ranges of threshold probabilities for 1-, 3-, and 5-year CVD, respectively.ConclusionThis study was the first to analyze the CIF and risk factors for CVD among CRC based on a competing-risk model. We have also built the first 1-, 3-, and 5-year competing nomogram for predicting CVD. This nomogram had excellent performance and could help clinicians to provide individualized management in clinical practice.

Section: Discussionmentioning

confidence: 99%

Cardiovascular Outcomes in the Patients With Colorectal Cancer: A Multi-Registry-Based Cohort Study of 197,699 Cases in the Real World

Wang

Front. Cardiovasc. Med.

et al. 2022

Front. Cardiovasc. Med.

“…The pharmacological or genetic inhibition of VEGF, and other key angiogenic signaling pathways accelerate the transition from adaptive cardiac remodeling to HF (60), while anti-angiogenic therapy beneficial to cancer (e.g., metastatic colon cancer, non-small cell lung cancer, breast cancer). However, cancer cells develop adaptive resistance to the antiangiogenic therapy as well as severe cardiotoxicity, leading to development of ischemic CVD and HF (61). Thus, angiogenesis delineates an auspicious substrate for both cancer and HF.…”

Section: Angiogenesismentioning

confidence: 99%

Evidence for reciprocal network interactions between injured hearts and cancer

Guler

Tscheiller

Sabater-Molina

et al. 2022

Self Cite

Heart failure (HF) and cancer are responsible for 50% of all deaths in middle-aged people. These diseases are tightly linked, which is supported by recent epidemiological studies and case control studies, demonstrating that HF patients have a higher risk to develop cancer such as lung and breast cancer. For HF patients, a one-size-fits-all clinical management strategy is not effective and patient management represents a major economical and clinical burden. Anti-cancer treatments-mediated cardiotoxicity, leading to HF have been extensively studied. However, recent studies showed that even before the initiation of cancer therapy, cancer patients presented impairments in the cardiovascular functions and exercise capacity. Thus, the optimal cardioprotective and surveillance strategies should be applied to cancer patients with pre-existing HF. Recently, preclinical studies addressed the hypothesis that there is bilateral interaction between cardiac injury and cancer development. Understanding of molecular mechanisms of HF-cancer interaction can define the profiles of bilateral signaling networks, and identify the disease-specific biomarkers and possibly therapeutic targets. Here we discuss the shared pathological events, and some treatments of cancer- and HF-mediated risk incidence. Finally, we address the evidences on bilateral connection between cardiac injury (HF and early cardiac remodeling) and cancer through secreted factors (secretoms).

“…On the other hand, vascular toxicity and dysfunction are frequent adverse effects of the currently applied anti-cancer therapy. New predictive and therapeutic strategies are strongly recommended for comprehensive secondary care considering the predictive approach, an aggressive antithrombotic treatment, and cost-effective protection tailored to the personalized patient profile [177,178]. To this end, phytochemicals have been demonstrated as being safe and potentially highly effective in protecting against non-physiologic inflammation, endothelial dysfunction, and cancer-associated stroke [19,[179][180][181].…”

Section: Cancer-associated Thrombosismentioning

confidence: 99%

Antithrombotic and antiplatelet effects of plant-derived compounds: a great utility potential for primary, secondary, and tertiary care in the framework of 3P medicine

et al. 2022

Thromboembolism is the third leading vascular disease, with a high annual incidence of 1 to 2 cases per 1000 individuals within the general population. The broader term venous thromboembolism generally refers to deep vein thrombosis, pulmonary embolism, and/or a combination of both. Therefore, thromboembolism can affect both – the central and peripheral veins. Arterial thromboembolism causes systemic ischemia by disturbing blood flow and oxygen supply to organs, tissues, and cells causing, therefore, apoptosis and/or necrosis in the affected tissues. Currently applied antithrombotic drugs used, e.g. to protect affected individuals against ischemic stroke, demonstrate significant limitations. For example, platelet inhibitors possess only moderate efficacy. On the other hand, thrombolytics and anticoagulants significantly increase hemorrhage. Contextually, new approaches are extensively under consideration to develop next-generation antithrombotics with improved efficacy and more personalized and targeted application. To this end, phytochemicals show potent antithrombotic efficacy demonstrated in numerous in vitro, ex vivo, and in vivo models as well as in clinical evaluations conducted on healthy individuals and persons at high risk of thrombotic events, such as pregnant women (primary care), cancer, and COVID-19-affected patients (secondary and tertiary care). Here, we hypothesized that specific antithrombotic and antiplatelet effects of plant-derived compounds might be of great clinical utility in primary, secondary, and tertiary care. To increase the efficacy, precise patient stratification based on predictive diagnostics is essential for targeted protection and treatments tailored to the person in the framework of 3P medicine. Contextually, this paper aims at critical review toward the involvement of specific classes of phytochemicals in antiplatelet and anticoagulation adapted to clinical needs. The paper exemplifies selected plant-derived drugs, plant extracts, and whole plant foods/herbs demonstrating their specific antithrombotic, antiplatelet, and fibrinolytic activities relevant for primary, secondary, and tertiary care. One of the examples considered is antithrombotic and antiplatelet protection specifically relevant for COVID-19-affected patient groups.