scholarly journals Inflammation in Atherosclerosis—No Longer a Theory

2021 ◽  
Author(s):  
Peter Libby
Keyword(s):  
Clinical Trials ◽  
Cardiovascular Events ◽  
Recurrent Events ◽  
Interleukin 1 ◽  
Medical Science ◽  
Experimental Investigations ◽  
Stable Phase ◽  
Coronary Syndrome ◽  
Inflammatory Status ◽  
Anti Inflammatory

Abstract Background Inflammation links to atherosclerosis and its complications in various experimental investigations. Animal studies have implicated numerous inflammatory mediators in the initiation and complication of atherosclerosis. Numerous studies in humans have shown associations of biomarkers of inflammation with cardiovascular events provoked by atheromata. Inflammatory status, determined by the biomarker C-reactive protein, can guide the allocation of statin therapy to individuals without elevated low-density lipoprotein (LDL) concentrations to prevent first ever adverse cardiovascular events. Content Until recently, no direct evidence has shown that an intervention that selectively limits inflammation can improve outcomes in patients with atherosclerosis. A recent study, based on decades of preclinical investigation, treated patients who had sustained a myocardial infarction and whose LDL was well-controlled on statin treatment with an antibody that neutralizes interleukin-1 beta. This trial, conducted in over 10 000 individuals, showed a reduction in major adverse cardiac events, establishing for the first time the clinical efficacy of an anti-inflammatory intervention in atherosclerosis. Two large subsequent studies have shown that colchicine treatment can also prevent recurrent events in patients recovering from an acute coronary syndrome or in the stable phase of coronary artery disease. These clinical trials have transformed inflammation in atherosclerosis from theory to practice. Summary Much work remains to optimize further anti-inflammatory interventions, minimize unwanted actions, and refine patient selection. This long road from discovery in the laboratory to successful clinical trials represents a victory for medical science, and opens a new avenue to reducing the risk that remains despite current treatments for atherosclerosis.

Inhibition of Interleukin-1 in the Treatment of Selected Cardiovascular Complications

2020 ◽  
Vol 15 ◽  
Author(s):  
Fatemeh Sadat Heydari ◽  
Simin Zare ◽  
Ali Roohbakhsh
Keyword(s):  
Clinical Trials ◽  
Standard Dose ◽  
Case Reports ◽  
Interleukin 1 ◽  
Cardiovascular Complications ◽  
Cardiovascular Disorders ◽  
Beneficial Effects ◽  
Coronary Syndrome ◽  
Cellular Inflammatory Response ◽  
Comprehensive Search

Background: Interleukin-1 (IL-1) is a pro-inflammatory cytokine that is produced by endothelial cells, smooth muscle cells, and macrophages. It is an important regulator of a complex humoral and cellular inflammatory response. IL1β is known to be implicated in the development of chronic inflammatory disorders such as rheumatoid arthritis. We aimed to review the effects of IL-1β antagonists in various cardiovascular disorders and to discuss their effectiveness in such diseases. Methods: Major biomedical databases, including PubMed and Scopus, were searched for clinical studies regarding the treatment of cardiovascular diseases (CVD) using IL-1β antagonists. Results: The drugs currently used in clinical trials are anakinra, the monoclonal antibodies canakinumab and gevokizumab, and the soluble decoy receptor rilonacept. There are clinical trials and case reports of patients with CVD in which anakinra administration, at the standard dose, has caused rapid clinical improvement and recovery in a few months. Our comprehensive search revealed that IL-1β antagonists have beneficial effects in the treatment of various cardiovascular disorders such as myocarditis, pericarditis, heart failure, acute coronary syndrome, myocardial infarction, atherosclerosis, and Kawasaki disease. Conclusion: The present review article shows that IL-1β has a major role in the pathophysiology of cardiovascular disorders, its antagonists have beneficial effects in these conditions, and their use should be considered in future studies.

scholarly journals Heart Protection by Herb Formula BanXia BaiZhu TianMa Decoction in Spontaneously Hypertensive Rats

2019 ◽  
Vol 2019 ◽  
pp. 1-10
Author(s):  
Jiaye Jiang ◽  
Dan Huang ◽  
Yuan Li ◽  
Zhongyuan Gan ◽  
Hanqing Li ◽  
...  
Keyword(s):  
Scientific Evidence ◽  
Interleukin 1 ◽  
Pharmacological Action ◽  
Nuclear Factor Κb ◽  
Left Ventricular ◽  
Inflammatory Status ◽  
Heart Protection ◽  
Anti Inflammatory

Modern research has shown that BanXia BaiZhu TianMa decoction (BBT) has the potential effect of lowering BP in vitro and in vivo. However, its therapeutic mechanism has not been clearly defined. The present study was designed to evaluate the protective effect of BBT on the heart by examining heart functioning and anti-inflammatory characteristics and to obtain scientific evidence for its further medical applications. BBT was extracted by decocting the herb extraction and analysed by HPLC. The left ventricular mass index (LVMI) was measured, and a histological examination of samples of the heart was performed. Inflammatory status was investigated by measuring tissue levels of interleukin-1 (IL-1), interleukin-6 (IL-6), tumour necrosis factor (TNF-α), inducible nitric oxide synthase (iNOS), and molecules of the nuclear factor κB (NF-κB) pathway. The BBT treatment significantly reversed the course of hypertension-derived heart damage. Meanwhile, the herb formula markedly reduced levels of IL-1, IL-6, TNF-α, and iNOS. In addition, the traditional compound suppressed the activity of the NF-κB pathway. The present study provides evidence of heart protection by BBT in SHRs. The action mechanisms may be partially attributable to the anti-inflammatory characteristic of the formula. Understanding the pharmacological action of BBT will benefit its impending use.

scholarly journals Prevention of ischaemic events in subjects with polydistrict vascular disease

2021 ◽  
Vol 23 (Supplement_E) ◽  
pp. E103-E108
Author(s):  
Giuseppe Patti ◽  
Chiara Ghiglieno
Keyword(s):  
Cardiovascular Events ◽  
Recurrent Events ◽  
Low Dose ◽  
Antiplatelet Agent ◽  
Multivessel Coronary Artery Disease ◽  
Thrombotic Risk ◽  
Coronary Syndrome ◽  
Artery Disease ◽  
Net Clinical Benefit ◽  
The Individual

Abstract The incidence of new cardiovascular events in patients with chronic coronary syndrome remains high, particularly in the presence of concomitant high thrombotic risk factors (diabetes mellitus, renal failure, multivessel coronary artery disease, multiple district atherosclerosis, recurrent events, heart failure). The risk of such recurrent events can be reduced by implementing various strategies, which include careful individual stratification of ischaemic and haemorrhagic risk and the choice of the most appropriate antithrombotic therapy for the individual patient, also by combining aspirin with a second antiplatelet agent/a low-dose anticoagulant, in order to achieve the maximum net clinical benefit.

scholarly journals Cardiovascular risk and inhibition of cyclooxygenase: traditional nonsteroidal anti-inflammatory drugs and cyclooxygenase-2 inhibitors

2013 ◽  
pp. 37-54
Author(s):  
M. Campanini ◽  
G. Mathieu
Keyword(s):  
Clinical Trials ◽  
Cardiovascular Risk ◽  
Cardiac Failure ◽  
Cardiovascular Events ◽  
Meta Analysis ◽  
Cardiovascular Effects ◽  
Cardiovascular Toxicity ◽  
Thrombotic Risk ◽  
Inflammatory Drugs ◽  
Anti Inflammatory

BACKGROUND The development of non-selective nonsteroidal anti-inflammatory drugs (tNSAIDs) and, more recently, of selective inhibitors of the cycloooxygenase-2 isoform (COXIBs), has contributed greatly towards the effective management of patients with arthritis and pain complaints. Although COXIBs have demonstrated an improved gastrointestinal tolerability compared with tNSAIDs, the cardiovascular effects of the two drugs types are much controversial. By blocking prostacyclin formation but leaving platelet-derived thromboxane A2 generation unopposed, the potential gastrointestinal benefit of COXIBs may come at cost of increased thrombotic risk. AIM OF THE STUDY This review aims at analysing the cardiovascular effects of the tNSAIDs and COXIBs. METHOD This review addresses the controversy of effects of COXIBs and tNSAIDs in 4 segments. It begins with a discussion about pathophysiological effects of cyclooxygenase inhibition on cardiovascular system. This is followed by a systematic review and meta-analysis of a control, randomized, double blind study and population-based matched case-control study to compare the risk of serious cardiovascular events with tNSAIDs and COXIBs. Then it answers to key questions with the aim to assist the clinicians for a systematic approach to evaluate the risk-benefit-ratio of NSAIDs in the clinical practice. Finally we analyse the open questions associated with the use of NSAIDs and the cardiovascular events. RESULTS The use of rofecoxib demonstrated an increase in adverse cardiovascular events. This toxic effect is not dose-related. The relationship between celecoxib and cardiovascular risk is less clear. The results of different clinical trials are conflicting: some didn’t demonstrate increase in cardiovascular toxicity but the APC study and recently a metanalysis reported a significant incidence of adverse cardiovascular events. Also valdecoxib and parecoxib appear to have increased risk for cardiovascular toxicity. Eterocoxib is still the object of three ongoing clinical trials. The TARGET study demonstrated for lumiracoxib a low increase in cardiovascular events compared with ibuprofen and naproxen. Also the use of ibuprofen (800 mg t.i.d.), diclofenac (75 mg b.i.d.) and indomethacin is reported to cause adverse cardiovascular events. The use of naprosen shows a better profile regarding cardiovascular toxicity. tNSAIDSs can worse clinical condition of patients affected by chronic cardiac failure and rofecoxib but not celecoxib can disclose clinical cardiac failure. A politherapy with both tNSAIDs and rofecoxib demonstrated an increase of blood arterial pressure and peripheral oedema. CONCLUSIONS This review confirms the findings from randomized trials, meta-analysis and observational studies regarding the risk of cardiovascular events with rofecoxib, valdecoxib e parecoxib, whereas the evidence for other COXIBs is not so clear. Also in the class of tNSAID some drugs (diclofenac and ibuprofen) can have an increased cardiovascular toxicity.

scholarly journals Inflammation and Comorbidity. Are There any Chances to Improve the Prognosis in Patients with Extremely High Cardiovascular Risk?

2021 ◽  
Vol 17 (4) ◽  
pp. 606-611
Author(s):  
M. V. Zykov ◽  
O. L. Barbarash
Keyword(s):  
Clinical Trial ◽  
Cardiovascular Risk ◽  
Cardiovascular Events ◽  
Clinical Evidence ◽  
High Cardiovascular Risk ◽  
Inflammatory Cascade ◽  
Coronary Syndrome ◽  
Trial Protocols ◽  
Anti Inflammatory ◽  
Special Category

The review contains actual data on possible approaches aimed at improving the prognosis in a special category of patients with extremely high cardiovascular risk, as well as in patients with recent acute coronary syndrome combined with comorbidity, including multifocal atherosclerosis. Currently, there are no class I recommendations for such patients aimed at reducing the risk of adverse cardiovascular events. It is suggested that suppression of inflammation may be a new therapeutic goal in this category of patients. Given the importance of inflammation in the development and course of atherosclerosis, in recent years there have been repeated attempts to influence the various components of the pro-inflammatory cascade involved in atherogenesis, but not all of them have been successful. Special attention is given to the anti-inflammatory effects of colchicine, a drug that can improve cardiovascular outcomes in patients with proven atherosclerosis. The review provides numerous pathogenetic and clinical evidence for the effectiveness of colchicine in patients with various manifestations of atherosclerosis. It is concluded that colchicine is the most promising anti-inflammatory drug that can improve the outcome of cardiovascular diseases. Thus, there is a need to initiate new clinical trial protocols aimed at studying the anti-inflammatory potential of this drug in patients with extreme cardiovascular risk.

scholarly journals MCP-1 Predicts Recurrent Cardiovascular Events in Patients with Persistent Inflammation

2021 ◽  
Vol 10 (5) ◽  
pp. 1137
Author(s):  
Luis M. Blanco-Colio ◽  
Nerea Méndez-Barbero ◽  
Ana María Pello Lázaro ◽  
Álvaro Aceña ◽  
Nieves Tarín ◽  
...  
Keyword(s):  
Plasma Levels ◽  
Cardiovascular Events ◽  
Recurrent Events ◽  
Primary Outcome ◽  
Troponin I ◽  
Monocyte Chemoattractant Protein 1 ◽  
Coronary Syndrome ◽  
Persistent Inflammation ◽  
Increased Risk ◽  
Galectin 3

Clinical data indicate that patients with C-reactive protein (CRP) levels higher than 2 mg per liter suffer from persistent inflammation, which is associated with high risk of cardiovascular disease (CVD). We determined whether a panel of biomarkers associated with CVD could predict recurrent events in patients with low or persistent inflammation and coronary artery disease (CAD). We followed 917 patients with CAD (median 4.59 ± 2.39 years), assessing CRP, galectin-3, monocyte chemoattractant protein-1 (MCP-1), N-terminal fragment of brain natriuretic peptide (NT-proBNP) and troponin-I plasma levels. The primary outcome was the combination of cardiovascular events (acute coronary syndrome, stroke or transient ischemic event, heart failure or death). Patients with persistent inflammation (n = 343) showed higher NT-proBNP and MCP-1 plasma levels compared to patients with CRP < 2 mg/L. Neither MCP-1 nor NT-proBNP was associated with primary outcome in patients with CRP < 2 mg/L. However, NT-proBNP and MCP-1 plasma levels were associated with increased risk of the primary outcome in patients with persistent inflammation. When patients were divided by type of event, MCP-1 was associated with an increased risk of acute ischemic events. A significant interaction between MCP-1 and persistent inflammation was found (synergy index: 6.17 (4.39–7.95)). In conclusion, MCP-1 plasma concentration is associated with recurrent cardiovascular events in patients with persistent inflammation.

scholarly journals Anti-Inflammatory Drugs in Patients with Ischemic Heart Disease

2021 ◽  
Vol 10 (13) ◽  
pp. 2835
Author(s):  
Ana María Pello Lázaro ◽  
Luis M. Blanco-Colio ◽  
Juan Antonio Franco Peláez ◽  
José Tuñón
Keyword(s):  
Clinical Trials ◽  
Acetylsalicylic Acid ◽  
Cardiovascular Events ◽  
Randomized Clinical Trials ◽  
Renin Angiotensin System ◽  
Clinical Settings ◽  
Potential Candidate ◽  
Angiotensin System ◽  
Inflammatory Drugs ◽  
Anti Inflammatory

Inflammation has long been known to play a role in atherogenesis and plaque complication, as well as in some drugs used in therapy for atherosclerotic disease, such as statins, acetylsalicylic acid, and modulators of the renin-angiotensin system, which also have anti-inflammatory effects. Furthermore, inflammatory biomarkers have been demonstrated to predict the incidence of cardiovascular events. In spite of this, and with the exception of acetylsalicylic acid, non-steroidal anti-inflammatory drugs are unable to decrease the incidence of cardiovascular events and may even be harmful to the cardiovascular system. In recent years, other anti-inflammatory drugs, such as canakinumab and colchicine, have shown an ability to reduce the incidence of cardiovascular events in secondary prevention. Colchicine could be a potential candidate for use in clinical practice given its safety and low price, although the results of temporary studies require confirmation in large randomized clinical trials. In this paper, we discuss the evidence linking inflammation with atherosclerosis and review the results from various clinical trials performed with anti-inflammatory drugs. We also discuss the potential use of these drugs in routine clinical settings.

The present state of aspirin and clopidogrel resistance

2009 ◽  
Vol 29 (03) ◽  
pp. 285-290 ◽  
Author(s):  
K. E. Guyer
Keyword(s):  
Diagnostic Tests ◽  
Arterial Thrombosis ◽  
Cardiovascular Events ◽  
Treatment Success ◽  
Antiplatelet Agents ◽  
Antiplatelet Drug ◽  
Coronary Syndrome ◽  
Testing Method ◽  
Pharmacological Response ◽  
Platelet Physiology

SummaryAntiplatelet therapy has demonstrated significant clinical benefit in the treatment of acute coronary syndrome. However, as with any treatment strategy it has been unable to prevent all cardiovascular events. This is far from surprising when considering the complexity of arterial thrombosis and more specifically platelet physiology. This lack of treatment success has provoked the introduction of various diagnostic tests and testing platforms with the intent of guiding and optimizing clinical treatment. Such tests have resulted in the generation of clinical data that suggest suboptimal response to antiplatelet agents such as aspirin and clopidogrel.In the case of both aspirin and clopidogrel, this suboptimal response has been termed resistance. Drug resistance would imply a lack of pharmacological response that has not been specifically investigated in many of the clinical studies performed to date. Rather, the term resistance has been used to describe various facets of platelet activation and aggregation relative to the testing method. Many of these measured parameters are not addressed in the therapeutic intent of the antiplatelet drug in question.

Antioxidant and Anti-inflammatory Activities of Organic and Aqueous Extracts of Northeast Algerian Marrubium vulgare

2018 ◽  
Vol 16 (S1) ◽  
pp. S119-S129
Author(s):  
I. Namoune ◽  
B. Khettal ◽  
A.M. Assaf ◽  
S. Elhayek ◽  
L. Arrar
Keyword(s):  
Ethyl Acetate ◽  
Methanolic Extract ◽  
Ethyl Acetate Extract ◽  
Interleukin 1 ◽  
Total Phenolic ◽  
Dependent Manner ◽  
Aqueous Extracts ◽  
Traditional Use ◽  
Marrubium Vulgare ◽  
Anti Inflammatory

Marrubium vulgare (Lamiaceae) is frequently used in traditional medicine to treat many illnesses from ancient times. Its beneficial effects include antibacterial, antioedematogenic, and analgesic activities. This study was designed to evaluate the antioxidant and anti-inflammatory activities of organic and aqueous extracts of the leaves, the flowers, the stems, and the roots of Marrubium vulgare. The total phenolic and flavonoid contents as well as the antioxidant and the anti-inflammatory effects of methanol, chloroform, ethyl acetate, and aqueous extracts have been investigated by using different in-vitro methods. It was found that the ethyl acetate extract from Marrubium vulgare stems had the highest total phenolic content, while the ethyl acetate extract from the leaves yielded a high concentration of flavonoids. The ethyl acetate extract from the stems exhibited the highest activity in scavenging of 2,2-diphenyl- 1-picrylhydrazyl (DPPH), as well as in protecting erythrocytes. The leaves aqueous extract exhibited the highest ferrous chelating activity and its methanolic extract was found to be the strongest inhibitor of lipid peroxidation in β-carotene bleaching assay. The leaves chloroform extracts as well as the flowers methanol, chloroform, and ethyl acetate extracts were found to decrease the pro-inflammatory tumor necrosis factor alpha (TNF-α) cytokine levels in a dose-dependent manner. On the other hand, the flowers methanolic extract and the leaves methanol, ethyl acetate, and aqueous extracts decreased the interleukin-1 beta (IL- 1β) release. It was also found that the methanol extract from the flowers and the chloroform extract from the stems of Marrubium vulgare inhibited interleukin-8 (IL-8) release. This study provides a scientific basis for the traditional use of Marrubium vulgare as an anti-inflammatory agent and for the plant to be considered as an important resource of natural antioxidants.

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