scholarly journals The support of genetic evidence for cardiovascular risk induced by antineoplastic drugs

2020 ◽  
Vol 6 (42) ◽  
pp. eabb8543
Author(s):  
Hui Cui ◽  
Shengkai Zuo ◽  
Zipeng Liu ◽  
Huanhuan Liu ◽  
Jianhua Wang ◽  
...  

Cardiovascular dysfunction is one of the most common complications of long-term cancer treatment. Growing evidence has shown that antineoplastic drugs can increase cardiovascular risk during cancer therapy, seriously affecting patient survival. However, little is known about the genetic factors associated with the cardiovascular risk of antineoplastic drugs. We established a compendium of genetic evidence that supports cardiovascular risk induced by antineoplastic drugs. Most of this genetic evidence is attributed to causal alleles altering the expression of cardiovascular disease genes. We found that antineoplastic drugs predicted to induce cardiovascular risk are significantly enriched in drugs associated with cardiovascular adverse reactions, including many first-line cancer treatments. Functional experiments validated that retinoid X receptor agonists can reduce triglyceride lipolysis, thus modulating cardiovascular risk. Our results establish a link between the causal allele of cardiovascular disease genes and the direction of pharmacological modulation, which could facilitate cancer drug discovery and clinical trial design.


2010 ◽  
Vol 9 ◽  
pp. CIN.S3191 ◽  
Author(s):  
Christine Galustian ◽  
Angus G. Dalgleish

The discovery of effective cancer treatments is a key goal for pharmaceutical companies. However, the current costs of bringing a cancer drug to the market in the USA is now estimated at $1 billion per FDA approved drug, with many months of research at the bench and costly clinical trials. A growing number of papers highlight the use of data mining tools to determine associations between drugs, genes or protein targets, and possible mechanism of actions or therapeutic efficacy which could be harnessed to provide information that can refine or direct new clinical cancer studies and lower costs. This report reviews the paper by R.J. Epstein, which illustrates the potential of text mining using Boolean parameters in cancer drug discovery, and other studies which use alternative data mining approaches to aid cancer research.



2020 ◽  
pp. 5-11
Author(s):  
Yu. V. Zhernakova

A significant number of epidemiological studies have shown that hyperuricemia is highly associated with the risk of developing cardiovascular disease, chronic kidney disease, and diabetes. In this connection, increased attention is required to monitor serum uric acid levels in patients, not only from a rheumatological point of view, but also with regard to reducing cardiovascular and renal risks. This article is a review of studies on the association of hyperuricemia with cardiovascular risk and a new consensus for the management of patients with hyperuricemia and high cardiovascular risk, published in december 2019 by a group of experts of the Russian Medical Society for Arterial Hypertension, which, among other things, includes a management algorithm of this category of patients.



2012 ◽  
Vol 8 (1) ◽  
pp. 10 ◽  
Author(s):  
Roland Asmar ◽  

The worldwide morbidity and mortality burden of cardiovascular disease (CVD) is overwhelming and caused by increasing life expectancy and an epidemic of risk factors, including hypertension. Therapeutic options targeting different areas of the renin–angiotensin–aldosterone system (RAAS) to disrupt pathophysiological processes along the cardiovascular continuum are available. Angiotensin-converting enzyme (ACE) inhibitors are first-line treatments for CVD and angiotensin receptor blockers (ARBs) are suitable alternatives. Both ACE inhibitors and ARBs prevent CVD by lowering blood pressure (BP). Additionally, several studies have demonstrated that RAAS blockade can reduce cardiovascular risk beyond what might be expected from BP lowering alone. However, the ARBs are not all equally effective. Telmisartan is a long-lasting ARB that effectively controls BP over the full 24-hour period. Recently, the Ongoing telmisartan alone and in combination with ramipril global endpoint trial (ONTARGET) study showed that telmisartan reduces cardiovascular events in high cardiovascular risk patients similarly to the gold standard ACE inhibitor ramipril beyond BP lowering alone, but with a better tolerability. Based on the results of the ONTARGET and Telmisartan randomized assessment study in ACE intolerant subjects with cardiovascular disease (TRANSCEND) studies, telmisartan is indicated for the reduction of cardiovascular morbidity. This article aims to review current guidelines for the management of CVD and consider key data from clinical trials and clinical practice evaluating the role of telmisartan in CVD.



2013 ◽  
Vol 154 (43) ◽  
pp. 1709-1712 ◽  
Author(s):  
Csaba Móczár

Introduction: Cardiovascular risk assessment may help in the identification of symptom-free subjects with high cardiovascular risk. Aim: The author studied the correlation between SCORE and Reynolds risk assessment systems based on data from the cardiovascular risk screening program carried out in subjects without cardiovascular disease. Method: Data obtained from 4462 subjects (1977 men and 2485 women; mean age, 47,4 years) were analysed. The comparison was based on risk categories of the SCORE system. Results: There was a strong correlation between the two scoring systems in the low risk population (under <2% SCORE risk the Spearman rho = 1, p < 0.001). A weak correlation was found in the medium risk group (between 3–4% the Spearman rho = 0.59–0.49, p < 0.001 and between 10–14% the Spearman rho = 0.42, ns.) and a stronger correlation in the high risk group (>15% the Spearmen rho = 0.8, p = 0.017). When correlations were analysed in gender and age categories, the weakest correlation was detected in medium risk women over 40 years of age. In cases when the differences between the two scoring systems were significant, the hsCRP levels were significantly higher (4.1 vs. 5.67 mg/L, p < 0.001). Conclusions: Introduction of hsCRP into cardiovascular risk assessments can refine the risk status of symptom-free subjects, especially among intermediate risk middle-age women (two-step risk assessment). Orv. Hetil., 154 (43), 1709–1712.



Author(s):  
Noora Wael Rasheed ◽  
Ooroba Jameel Taresh

       Some studies indicated a relationship between increased serum levels of osteoprotegerin with arterial calcification and as a result, it leads to the risk of cardiovascular disease. In our study group we selected patients with osteoporosis, with similar age and body mass index for the assessment of the relationship between cardiovascular disease and osteoprotegerin serum level. We took into account the analysis of correlation and association between the presence of distinct patterns of atherosclerosis and associated diseases like high blood pressure,  diabetes mellitus, low HDL cholesterol, increased LDL cholesterol, increased triglycerides and was the case of presence of any type of dyslipidemia, in case of pre-existent treatment. Objective of study was the assessment of osteoprotegerin value as predictive marker for cardiovascular and metabolic risk in osteoporotic patients. Our results showed significant correlations of parathyroid hormone, osteocalcin and biochemical markers of bone with glucose metabolism and lipid were found in our research, maintaining crosstalk between calcium and biochemical markers of bone and cardiovascular risk. The serum level of Osteoprotegerin has been shown to have a large predictive value for the metabolic syndrome as a cardiovascular risk standard in patients with osteoporosis. The osteoprotegerin serum levels were increased in the patients with metabolic syndrome as a protective response facing the atherosclerotic lesions.



2016 ◽  
Vol 16 (19) ◽  
pp. 2107-2114 ◽  
Author(s):  
Haijun Chen ◽  
Jianlei Wu ◽  
Yu Gao ◽  
Haiying Chen ◽  
Jia Zhou


2020 ◽  
Vol 18 (5) ◽  
pp. 473-487 ◽  
Author(s):  
Charalampos Papagoras ◽  
Paraskevi V. Voulgari ◽  
Alexandros A. Drosos

The spondyloarthritides are a group of chronic systemic inflammatory joint diseases, the main types being ankylosing spondylitis (AS) and psoriatic arthritis (PsA). Evidence accumulating during the last decades suggests that patients with AS or PsA carry an increased risk for cardiovascular disease and cardiovascular death. This risk appears to be mediated by systemic inflammation over and above classical cardiovascular risk factors. The excess cardiovascular risk in those patients has been formally acknowledged by scientific organizations, which have called physicians’ attention to the matter. The application by Rheumatologists of new effective anti-rheumatic treatments and treat-to-target strategies seems to benefit patients from a cardiovascular point of view, as well. However, more data are needed in order to verify whether anti-rheumatic treatments do have an effect on cardiovascular risk and whether there are differences among them in this regard. Most importantly, a higher level of awareness of the cardiovascular risk is needed among patients and healthcare providers, better tools to recognize at-risk patients and, ultimately, commitment to address in parallel both the musculoskeletal and the cardiovascular aspect of the disease.



2020 ◽  
Vol 17 (9) ◽  
pp. 1102-1116
Author(s):  
Sudip Kumar Mandal ◽  
Utsab Debnath ◽  
Amresh Kumar ◽  
Sabu Thomas ◽  
Subhash Chandra Mandal ◽  
...  

Background and Introduction: Sesquiterpene lactones are a class of secondary metabolite that contains sesquiterpenoids and lactone ring as pharmacophore moiety. A large group of bioactive secondary metabolites such as phytopharmaceuticals belong to this category. From the Asteraceae family-based medicinal plants, more than 5,000 sesquiterpene lactones have been reported so far. Sesquiterpene lactone-based pharmacophore moieties hold promise for broad-spectrum biological activities against cancer, inflammation, parasitic, bacterial, fungal, viral infection and other functional disorders. Moreover, these moiety based phytocompounds have been highlighted with a new dimension in the natural drug discovery program worldwide after the 2015 Medicine Nobel Prize achieved by the Artemisinin researchers. Objective: These bitter substances often contain an α, β-unsaturated-γ-lactone as a major structural backbone, which in recent studies has been explored to be associated with anti-tumor, cytotoxic, and anti-inflammatory action. Recently, the use of sesquiterpene lactones as phytomedicine has been increased. This study will review the prospect of sesquiterpene lactones against inflammation and cancer. Methods: Hence, we emphasized on the different features of this moiety by incorporating its structural diversity on biological activities to explore structure-activity relationships (SAR) against inflammation and cancer. Results: How the dual mode of action such as anti-inflammatory and anti-cancer has been exhibitedby these phytopharmaceuticals will be forecasted in this study. Furthermore, the correlation of anti-inflammatory and anti-cancer activity executed by the sesquiterpene lactones for fruitful phytotherapy will also be revealed in the present review in the milieu of pharmacophore activity relation and pharmacodynamics study as well. Conclusion: So, these metabolites are paramount in phytopharmacological aspects. The present discussion on the future prospect of this moiety based on the reported literature could be a guide for anti-inflammatory and anti-cancer drug discovery programs for the upcoming researchers.



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