cardiovascular-agents and Arthritis--Rheumatoid

Although cardiac diseases such as acute myocardial infarction, heart failure and arrhythmias are the leading cause of cardiovascular complications in rheumatoid arthritis (RA), their pathogenesis is far from being understood and optimal therapeutic options to treat specifically these disorders in RA are lacking. Preclinical studies on animal models of arthritis can help to decipher the complex link between arthritis and the heart, and to identify critical pathways and novel therapeutic targets. This review presented the available data on cardiac disorders in animal models of RA, as well as the current knowledge on pathophysiology and pharmacology of these disorders. Future directions for translational studies in a cardiorheumatic perspective are proposed.

Topics: Animals; Antirheumatic Agents; Arthritis, Rheumatoid; Cardiovascular Agents; Disease Models, Animal; Heart Diseases; Humans; Inflammation Mediators; Joints; Myocardium; Oxidative Stress

Natural products, whether pure compounds or standardized plant extracts, offer unlimited opportunities for other drug sources due to the unequaled availability of chemical diversity. Stinging Nettle (Urtica dioica) is a unique herbaceous perennial flowering plant with stinging hairs. The leaf extract of nettle was one of the herbal remedies which the experimental, clinical and trials have complemented each other. It is a very well-known plant with a wide historical background use of stems, leaves and roots. It has a long history of use as power sources such as soup or curry, and also used as fiber and a medicinal plant. Urtica dioica has traditionally been used in the control of cardiovascular disorders especially hypertension. The leaf extract of Urtica dioica has been reported to improve glucose homeostasis in vivo. Nettle root could prevent some of the effects of prostatic hyperplasia. Extracts of nettle leaf are used as anti-inflammatory remedies for rheumatoid arthritis. Urtica dioica extract significantly increased the sensitivity of breast cancer cells to paclitaxel. This article aims to review the very wide ranging of pharmacological effects of Urtica dioica extract.. Articles on PuBmed between 1980 and 2019.. Description and critical review of the pharmacological effects of Urtica dioica and other uses.. The nettle is actually a plant with many qualities and uses. The interest in it is deserved and it is given by other studies and investigations.

Topics: Animals; Anti-Inflammatory Agents; Antineoplastic Agents; Antioxidants; Arthritis, Rheumatoid; Biological Products; Breast Neoplasms; Cardiovascular Agents; Drug Evaluation, Preclinical; Female; Humans; Male; Plant Extracts; Plant Leaves; Plant Roots; Prostatic Hyperplasia; Urtica dioica

Chronic wounds are a major cause of morbidity and mortality. Approximately 20% to 23% of nonhealing wounds that are refractory to vascular intervention have other causes, including vasculitis, pyoderma gangrenosum, and other autoimmune diseases. The purpose of this article was to review the literature across medical and surgical specialties with regard to refractory chronic wounds associated with vasculitis and autoimmune diseases and to delineate clinical outcomes of these wounds in response to vascular and other interventions.. An electronic search encompassing MEDLINE, PubMed, Cochrane Library, and Scopus was completed using the following search terms: rheumatoid arthritis; systemic sclerosis; systemic lupus erythematosus; antineutrophil cytoplasmic antibody-associated vasculitis; mixed connective tissue disease; antiphospholipid syndrome; pyoderma gangrenosum; thromboangiitis obliterans; cryoglobulinemia; hydroxyurea; sickle cell; atrophie blanche; livedoid vasculitis; cholesterol emboli; calciphylaxis; antiphospholipid antibodies; prothrombotic; combined with the terms: chronic wound and leg ulcer. Full-text articles published in English up to March 1, 2016, that investigated the clinical outcomes of chronic wounds associated with autoimmune diseases were included. Review articles and evaluations of management of chronic wounds were also reviewed. Primary outcomes included in the review were amputation, ulcer healing, reduction in wound size, overall survival, and freedom from reintervention. Owing to the heterogeneity of data reporting among articles, qualitative analysis is also reported.. Vasculitis and autoimmune diseases play a role in 20% to 23% of patients with chronic lower extremity ulcers. Furthermore, patients with autoimmune disease have a significantly high rate of split thickness skin graft failure (50% compared to 97% in patients without autoimmune disease; P = .0002). The management of leg ulcers associated with autoimmune diseases is discussed.. Autoimmune and vasculitic causes should be considered in patients with chronic wounds who do not respond to appropriate vascular intervention and standard local wound care. A multidisciplinary approach with the involvement of rheumatologists allows investigation for underlying systemic disease and improves clinical outcomes for many of these challenging patients.

Topics: Anemia, Sickle Cell; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Antiphospholipid Syndrome; Antirheumatic Agents; Antisickling Agents; Arthritis, Rheumatoid; Autoimmune Diseases; Calciphylaxis; Cardiovascular Agents; Chronic Disease; Cryoglobulinemia; Diagnosis, Differential; Embolism, Cholesterol; Erythema Nodosum; Humans; Hydroxyurea; Leg Ulcer; Panniculitis; Pyoderma Gangrenosum; Steroids; Thromboangiitis Obliterans; Vasculitis; Wound Healing

In recent years, the scientific community has gained significant insight into the complex interaction between inflammation and the cardiovascular system in patients with rheumatoid arthritis (RA), which leads to increased cardiovascular (CV) morbidity and mortality in these patients. Our common understanding of this association is that persistent inflammation contributes to the development of premature atherosclerosis. Consequently, the question arises whether control of inflammation with antirheumatic treatment will be able to improve CV outcome. While there are a lot of data that demonstrate improvement of numerous CV surrogate markers in patients treated with virtually all antirheumatic drug classes, there is much less information about the possible translation of these beneficial effects into improved CV outcome. In summary, the published evidence suggests that tumor necrosis factor (TNF) alpha inhibitors may improve CV outcome. The same is true for methotrexate (MTX). However, it is not clear whether MTX works via suppression of inflammation or through drug specific mechanisms. For other traditional disease-modifying antirheumatic drugs and biologic therapies, there are no convincing data for improved CV outcome. Only a few drugs (glucocorticoids and NSAIDs) have been associated with increased CV risk. Treating RA aggressively, as recommended by current guidelines, is likely to have a beneficial effect on CV outcomes.

Topics: Animals; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Antirheumatic Agents; Arthritis, Rheumatoid; Atherosclerosis; Cardiovascular Agents; Cardiovascular Diseases; Evidence-Based Medicine; Humans; Immunosuppressive Agents; Molecular Targeted Therapy; Rheumatoid Vasculitis; Treatment Outcome

Patients with Rheumatoid Arthritis (RA) and Systemic Lupus Erythematosus (SLE) have a significantly increased risk of cardiovascular disease (CVD). The reason for this is unclear but may be due, at least in part, to the failure of endothelial repair mechanisms. Over the last 15 years there has been much interest in the mechanisms of endothelial renewal and its potential as a therapy for CVD. In the circulation there are two distinct populations of cells; myeloid angiogenic cells (MACs) which augment repair by the paracrine secretion of angiogenic factors, and outgrowth endothelial cells (OECs) which are true endothelial progenitor cells (EPCs) and promote vasculogenesis by differentiating into mature endothelium. There are marked abnormalities in the number and function of these cells in patients with RA and SLE. Inflammatory cytokines including interferon-alpha (IFNα) and tumour-necrosis factor alpha (TNFα) both impair MAC and OEC function ex vivo and may therefore contribute to the CVD risk in these patients. Whilst administration of mononuclear cells, MACs and other progenitors has improved cardiovascular outcomes in the acute setting, this is not a viable option in chronic disease. The pharmacological manipulation of MAC/OEC function in vivo however has the potential to significantly improve endothelial repair and thus reduce CVD in this high risk population.

Topics: Angiogenic Proteins; Animals; Arthritis, Rheumatoid; Cardiovascular Agents; Cardiovascular Diseases; Endothelial Cells; Humans; Immunosuppressive Agents; Inflammation Mediators; Lupus Erythematosus, Systemic; Regeneration; Stem Cell Transplantation; Stem Cells

Focal adhesions (FA) are important mediators of endothelial cytoskeletal interactions with the extracellular matrix (ECM) via transmembrane receptors, integrins and integrin-associated intracellular proteins. This communication is essential for a variety of cell processes including EC barrier regulation and is mediated by the non-receptor protein tyrosine kinase, focal adhesion kinase (FAK). As FA mediate the basic response of EC to a variety of stimuli and FAK is essential to these responses, the idea of targeting EC FAK as a therapeutic strategy for an assortment of diseases is highly promising. In particular, inhibition of FAK could prove beneficial in a variety of cancers via effects on EC proliferation and angiogenesis, in acute lung injury (ALI) via the attenuation of lung vascular permeability, and in rheumatoid arthritis via reductions in synovial angiogenesis. In addition, there are potential therapeutic benefits of FAK inhibition in cardiovascular disease and diabetic nephropathy as well. Several drugs that target EC FAK are now in existence and include agents currently under investigation in preclinical models as well as drugs that are readily available such as the sphingolipid analog FTY720 and statins. As the role of EC FAK in the pathogenesis of a variety of diseases continues to be explored and new insights are revealed, drug targeting of FAK will continue to be an important area of investigation and may ultimately lead to highly novel and effective strategies to treat these diseases.

Topics: Acute Lung Injury; Angiogenesis Inhibitors; Animals; Antirheumatic Agents; Arthritis, Rheumatoid; Cardiovascular Agents; Cardiovascular Diseases; Diabetic Nephropathies; Endothelial Cells; Focal Adhesion Protein-Tyrosine Kinases; Humans; Neoplasms; Neovascularization, Pathologic; Protein Kinase Inhibitors; Respiratory System Agents; Signal Transduction

Inflammatory pathways have been implicated in the initiation and progression of cardiovascular diseases. Accelerated atherosclerosis has been described in patients with chronic inflammatory diseases, particularly rheumatoid arthritis, disproportionate to individuals' detectable traditional vascular risk factors. This finding suggests that other pathways associated with inflammation might account for increased vascular risk in such diseases. Highly specific biologic agents can precisely block the activity of cytokines generated during inflammatory cascades; the effects of these inflammatory moieties on vascular physiology and overall risk of cardiovascular events has been directly evaluated. This review summarizes key epidemiologic, physiologic and model data, which together suggest that tumor necrosis factor, a pivotal cytokine in the inflammatory cascade, is directly involved in vascular pathophysiology and that its inhibition might confer an overall advantage to the recipient. Moreover, such data obtained in chronic inflammatory diseases likely have relevance to primary atherosclerosis.

Topics: Animals; Anti-Inflammatory Agents; Arteries; Arthritis, Rheumatoid; Atherosclerosis; Cardiovascular Agents; Chronic Disease; Elasticity; Endothelium, Vascular; Heart Failure; Humans; Inflammation; Inflammation Mediators; Insulin Resistance; Lipid Metabolism; Obesity; Registries; Risk Assessment; Risk Factors; Signal Transduction; Treatment Outcome; Tumor Necrosis Factor-alpha

Tumor necrosis factor (TNF)-alpha has been thoroughly investigated and established as a pivotal component of the inflammatory cascade. This review encompasses the safety and efficacy of TNF antagonists in rheumatoid arthritis, the interplay between rheumatoid arthritis and heart failure, as well as presentation of the available preclinical and clinical data discussing the use of anti-TNF therapy in patients with chronic heart failure. There is well-documented evidence for the role of anti-TNF-alpha in rheumatoid arthritis, in contrast to the controversial role of anti-TNF-alpha in heart failure. In animal models and small-scale clinical trials, anti-TNF therapy showed some promise in treating chronic heart failure, whereas larger, multicenter, randomized, placebo-controlled clinical trials (i.e., RECOVER [Research into Etanercept Cytokine Antagonism in Ventricular Dysfunction] and RENAISSANCE [Randomized Etanercept North American Strategy to Study Antagonism of Cytokines]) failed to show a statistically significant difference in composite clinical function score for anti-TNF therapy versus placebo. Future investigation is needed to determine if individualized dosing of anti-TNF therapy is necessary and whether or not treating patients with earlier-stage disease will show a benefit.

Topics: Animals; Antirheumatic Agents; Arthritis, Rheumatoid; Cardiovascular Agents; Chronic Disease; Disease Models, Animal; Heart Failure; Humans; Treatment Outcome; Tumor Necrosis Factor-alpha

Statins are pluripotent agents exhibiting multiple non-lipid-lowering actions. Besides their established role in the management of hypercholesterolemia, statins may also have beneficial actions in other pathological conditions, namely: a) osteoporosis and osteoporosis-related bone fractures, b) cancer, c) solid organ transplantation, d) cerebrovascular events (transient ischemic attack and stroke episodes), e) various neurological disorders, such as Alzheimer's disease, Parkinson's disease and multiple sclerosis, f) cardiac arrhythmias and heart failure, g) renal diseases, h) rheumatoid arthritis, i) autoimmune diseases, j) sepsis, and k) allergic asthma. We reviewed the literature searching for studies that support or oppose the use of statins in each proposed indication. In some of these emerging indications, a role for statin treatment is more firmly set; for others, current evidence is more controversial. Future trials may reveal more convincing evidence that will make statin use necessary in the therapeutic management of several diseases.

Topics: Animals; Anti-Asthmatic Agents; Antineoplastic Agents; Antirheumatic Agents; Arthritis, Rheumatoid; Asthma; Autoimmune Diseases; Bone Density Conservation Agents; Cardiovascular Agents; Cerebrovascular Disorders; Heart Diseases; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Kidney Diseases; Neoplasms; Nervous System Diseases; Neuroprotective Agents; Organ Transplantation; Osteoporosis; Sepsis

Chronic low-grade inflammation was recognized during the past decade as an important risk factor for the development of atherosclerosis and, more recently, for the development of heart failure. Patients with rheumatoid arthritis (RA) are at increased risk of morbidity and mortality from ischemic cardiovascular events and heart failure. Epidemiologic and clinical studies indicate that RA is an independent risk factor for cardiovascular disease, which suggests that chronic exposure to high levels of inflammatory mediators contributes to this enhanced risk. The relative contribution of conventional risk factors to the acceleration of cardiovascular disease does not seem to be increased in patients with RA compared with control populations. Nonetheless, some preclinical laboratory measures of risk factors (e.g. insulin sensitivity) are adversely modulated in the context of the highly inflammatory rheumatoid microenvironment. Discerning the net effect of RA therapies on cardiovascular disease is also challenging because, theoretically, their biologic effects could either promote or attenuate atherosclerosis and ventricular dysfunction; however, available data suggest a beneficial effect on cardiovascular morbidity and mortality in patients with RA. This review provides an overview of the potential influence of RA and its treatment on the development and progression of cardiovascular disease, and outlines some preliminary recommendations for prevention and management of this complication in patients with RA.

Topics: Antirheumatic Agents; Arthritis, Rheumatoid; Cardiovascular Agents; Cardiovascular Diseases; Disease Progression; Humans; Incidence; Prevalence; Prognosis; Risk Factors

Topics: Adrenergic beta-Antagonists; Analgesics; Angiotensin-Converting Enzyme Inhibitors; Anti-Arrhythmia Agents; Antibiotics, Antineoplastic; Antihypertensive Agents; Arthritis, Rheumatoid; Calcium Channel Blockers; Cardiotonic Agents; Cardiovascular Agents; Humans; Hypoglycemic Agents; Insulin; Interferons; Mitoguazone; Narcotics; Pharmacology; Piperazines; Receptors, Dopamine; Retinoids

Topics: Adjuvants, Immunologic; Analgesics; Anesthetics; Animals; Antineoplastic Agents; Arthritis, Rheumatoid; Cardiovascular Agents; Gallbladder; Humans; Hypnotics and Sedatives; Immunosuppressive Agents; Liver; Muscle Relaxants, Central; Narcotics; Pharmaceutical Preparations; Research; Respiration

Patients with rheumatoid arthritis (RA) have an increased risk of coronary artery disease (CAD) above the baseline. Baicalin possesses beneficial effects against both RA and CAD, but little is know on its clincial efficacy among patients manifesting both CAD and RA.. Three hundred seventy four patients with CAD and RA were randomized to receive either 500 mg baicalin or placebo orally everyday for 12 weeks. Lipid profile, cardiotrophin-1 (CT-1), high sensitivity C-reactive protein (hs-CRP), European League Against Rheumatism (EULAR) response were analyzed at the end of study period.. After 12 week treatment, levels of triglycerides, total cholesterol, LDL-cholesterol and apolipoproteins, as well as CT-1 and hs-CRP, were all significantly improved in the baicalin group compared to the placebo group (1.12 ± 0.36 vs 1.87 ± 0.46 mmol/L, 2.87 ± 1.23 vs 3.22 ± 1.07 mmol/L, 1.38 ± 0.41 vs 1.16 ± 0.32 mmol/L, 1.31 ± 0.41 vs 1.23 ± 0.29 g/L, 42.9 ± 13.7 vs 128.4 ± 24.3 ng/mL, 1.64 ± 0.38 vs 3.9 ± 1.4 mg/dL, respectively). Significantly higher proportion of patients in the baicalin group (71%) reported good/moderate EULAR response than the placebo group (53%).. Baicalin reduces blood lipids and inflammation in patients with both CAD and RA, supporting its further clinical application.

Topics: Administration, Oral; Antirheumatic Agents; Apolipoproteins; Arthritis, Rheumatoid; C-Reactive Protein; Cardiovascular Agents; Coronary Artery Disease; Cytokines; Double-Blind Method; Drug Administration Schedule; Female; Flavonoids; Humans; Lipoproteins, HDL; Lipoproteins, LDL; Male; Middle Aged; Treatment Outcome; Triglycerides

Rheumatoid arthritis is a systemic inflammatory condition associated with increased cardiovascular risk that may be due to underlying endothelial dysfunction and subsequent aortic stiffening. We hypothesized that supplementation with tetrahydrobiopterin (BH4) would recouple endothelial nitric oxide synthase and thus improve endothelial function and consequently reduce aortic stiffness.. We conducted 2 randomized, double-blinded, placebo-controlled crossover studies examining 2 separate regimens: an acute regimen, with a single dose of BH4 400 mg versus placebo (n=18), and a short-term regimen, composed of a 1-week treatment with BH4 400 mg once daily versus placebo (n=15). Flow-mediated dilatation and aortic pulse wave velocity were studied 4 times, before and after each treatment phase. Acute BH4 supplementation led to an improvement of flow-mediated dilatation, whereas placebo had no effect (mean±SD of effect difference 2.56±4.79%; P=0.03). Similarly, 1-week treatment with BH4 improved endothelial function, but there was no change with placebo (mean±SD of effect difference 3.50±5.05%; P=0.02). There was no change in aortic pulse wave velocity following acute or short-term BH4 supplementation or placebo (mean±SD of effect difference: acute 0.09±0.67 m/s, P=0.6; short-term 0.03±1.46 m/s, P=0.9).. Both acute and short-term supplementation with oral BH4 improved endothelial function but not aortic stiffness. This result suggests that BH4 supplementation may be beneficial for patients with rheumatoid arthritis by improving endothelial dysfunction and potentially reducing risk of cardiovascular disease. There appears to be no causal relationship between endothelial function and aortic stiffness, suggesting that they occur in parallel, although they may share common risk factors such as inflammation.

Topics: Administration, Oral; Adult; Aged; Arthritis, Rheumatoid; Biomarkers; Biopterins; Cardiovascular Agents; Cross-Over Studies; Dietary Supplements; Double-Blind Method; Drug Administration Schedule; Endothelium, Vascular; England; Female; Humans; Inflammation Mediators; Male; Middle Aged; Nitric Oxide Synthase Type III; Pilot Projects; Pulse Wave Analysis; Time Factors; Treatment Outcome; Vascular Diseases; Vascular Stiffness; Vasodilation; Young Adult

Topics: Adrenal Cortex Hormones; Anticoagulants; Arthritis, Rheumatoid; Cardiovascular Agents; Echocardiography, Doppler; Female; Heart Failure; Humans; Immunosuppressive Agents; Middle Aged; Predictive Value of Tests; Recovery of Function; Stroke Volume; Thrombosis; Time Factors; Treatment Outcome; Ventricular Function, Left

Topics: Arthritis, Rheumatoid; Cardiovascular Agents; Cardiovascular Diseases; Cause of Death; Female; Follow-Up Studies; Forecasting; Humans; Incidence; Male; Mass Screening; Middle Aged; Netherlands; Prospective Studies; Risk Assessment; Risk Management; Survival Rate

The development of an autoantibody to human Factor VIII is rare and presents many problems for diagnosis and treatment. We have seen several cases at our institution recently with widely heterogenous clinical and laboratory presentations. A wide range of treatment modalities were used in these cases with no gold standard of treatment or widely accepted guidelines existing. This has prompted us to examine all cases of this condition presenting at Fremantle Hospital over the last decade. We describe four cases which demonstrate the heterogeneity of this condition and its treatment and review the recent literature on the subject.

Topics: Adult; Aged; Aged, 80 and over; Arthritis, Rheumatoid; Autoantibodies; Autoimmune Diseases; Azathioprine; Breast Neoplasms; Cardiovascular Agents; Cardiovascular Diseases; Chlorambucil; Cyclophosphamide; Factor VIII; Female; Hematoma; Hemophilia A; Humans; Immunoglobulin G; Immunosuppressive Agents; Infections; Leukemia, Lymphocytic, Chronic, B-Cell; Male; Neoplasms, Multiple Primary; Partial Thromboplastin Time; Prednisolone; Retrospective Studies

Topics: Arthritis; Arthritis, Rheumatoid; Capillaries; Capillary Resistance; Cardiovascular Agents; Dihydroergotamine; Ergot Alkaloids; Gold

Four new derivatives of hydrocortisone, each containing in common a methyl grouping at the 16a-carbon position of the steroid molecule, have been synthesized and are being studied in human subjects. The compounds are 16a-methyl 9a-fluoroprednisolone (MK-125: hexadecadrol), 16a-methyl 9a-fluorohydrocortisone (MK-126), 16a-methylprednisolone (MK-110), and 16a-methylhydrocortisone (MK-117). Biologic tests in animals have indicated that these analogues exhibit, in varying degrees, striking alterations of several physiologic properties, including enhanced anti-inflammatory activity unassociated with corresponding disturbance of electrolyte metabolism. In the present study preliminary observations of the effects of the four new compounds were made in patients with rheumatoid arthritis. Clinical estimates of the antirheumatic potencies of the compounds, as compared with prednisolone, were accomplished by determining the milligram dosages required to maintain similar degrees of improvement of active rheumatoid manifestations. The approximate antirheumatic potencies of the compounds, on an average, were gauged as follows: for 16a-methyl 9a-fluoroprednisolone, about seven times greater than prednisolone; for 16a-methyl 9a-fluorohydrocortisone, about three times greater; for 16a-methylprednisolone, approximately one-third greater; and for 16a-methylhydrocortisone, about 70 per cent that of prednisolone. In the dosage used, none of the compounds promoted discernible salt and water retention. These observations would indicate that 16a-methyl 9a-fluoroprednisolone (hexadecadrol) possesses greater anti-inflammatory potency per milligram than any steroid yet produced. The therapeutic efficiency of the compound on longterm administration is being studied.

Topics: Animals; Anti-Inflammatory Agents; Antirheumatic Agents; Arthritis, Rheumatoid; Cardiovascular Agents; Dermatologic Agents; Dexamethasone; Edema; Glucocorticoids; Humans; Hydrocortisone; Methylprednisolone; Prednisolone

Topics: Arthritis; Arthritis, Rheumatoid; Cardiovascular Agents; Hexamethonium; Muscle Relaxants, Central