cardiovascular-agents and Aortic-Aneurysm--Abdominal

Abdominal aortic aneurysms (AAA) pose a considerable health burden and at present are only managed surgically since there is no proven pharmacotherapy that will retard their expansion or reduce the incidence of fatal rupture. This pathology shares several pathophysiological mechanisms with atherosclerosis, such as macrophage infiltration, inflammation, and degradation of extracellular matrix. Therefore, therapeutic targets proven effective in the treatment of atherosclerosis could also be considered for treatment of AAA. Different members of the nuclear receptor (NR) superfamily have been extensively studied as potential targets in the treatment of cardiovascular disease (CVD) and therefore might also be suited for AAA treatment. In this context, this review summarizes the role of different NRs in CVD, mostly atherosclerosis, and discusses in detail the current knowledge of their implications in AAA. From this overview it becomes apparent that NRs that were attributed a beneficial or adverse role in CVD have similar roles in AAA. Together, this overview provides compelling evidence to consider several NRs as attractive targets for future treatment of AAA.

Topics: Animals; Aorta, Abdominal; Aortic Aneurysm, Abdominal; Atherosclerosis; Cardiovascular Agents; Humans; Receptors, Cytoplasmic and Nuclear; Signal Transduction

Abdominal aortic aneurysm (AAA) rupture is an important cause of death in adults. Currently, the only treatment for AAA is open or endovascular surgical repair. In most parts of the developed world, AAAs can be identified at an early stage as a result of incidental imaging and screening programmes. Randomized clinical trials have demonstrated that early elective surgical repair of these small AAAs is not beneficial, and an unmet clinical need exists to develop medical therapies for small AAAs that limit or prevent the progressive expansion and rupture of the aneurysm. A large amount of research is currently being performed to increase the understanding of AAA pathogenesis and ultimately lead to the development of medical therapies, such as drug-based and cell-based strategies for this disease. This Review summarizes the latest research findings and current theories on AAA pathogenesis, including discussion of the pros and cons of current rodent models of AAA, and highlights potential medical therapies for AAA, summarizing previous, ongoing and potential clinical trials of medical interventions for small AAAs. This expanding volume of research on AAA is expected to result in a range of novel medical therapies for AAA within the next decade.

Topics: Animals; Aortic Aneurysm, Abdominal; Aortic Rupture; Cardiovascular Agents; Disease Models, Animal; Humans; Molecular Targeted Therapy; Risk Factors; Stem Cell Transplantation; Treatment Outcome

Abdominal aortic aneurysm (AAA), a progressive segmental abdominal aortic dilation, is associated with high mortality. AAA is characterized by inflammation, smooth muscle cell (SMC) depletion and extracellular matrix (ECM) degradation. Surgical intervention and endovascular therapy are recommended to prevent rupture of large AAAs. Unfortunately, there is no reliable pharmacological agent available to limit AAA expansion. In the past decades, extensive investigations and a body of ongoing clinical trials aimed at defining potent treatments to inhibit and even regress AAA growth.. In this review, we summarized recent progress of potential strategies, particularly macrolides, tetracyclines, statins, angiotensin converting enzyme inhibitors, angiotensin receptor blocker, corticosteroid, anti-platelet drugs and mast cell stabilizers. We also consider recently identified novel molecular targets, which have potential to be translated into clinical practice in the future.

Topics: Animals; Aorta, Abdominal; Aortic Aneurysm, Abdominal; Cardiovascular Agents; Dilatation, Pathologic; Disease Progression; Humans; Risk Factors; Treatment Outcome

Abdominal aortic aneurysm (AAA) is a vascular disease with high mortality. Because of the lack of effective medications to stop or reverse the progression of AAA, surgical operation has become the most predominant recommendation of treatment for patients. There are many potential mechanisms, including inflammation, smooth muscle cell apoptosis, extracellular matrix degradation, oxidative stress, and so on, involving in AAA pathogenesis. According to those mechanisms, some potential therapeutic drugs have been proposed and tested in animal models and even in clinical trials. This review focuses on recent advances in both pathogenic mechanisms and potential pharmacologic therapies of AAA.

Topics: Age Factors; Aged; Animals; Aorta, Abdominal; Aortic Aneurysm, Abdominal; Cardiovascular Agents; Comorbidity; Dilatation, Pathologic; Female; Humans; Male; Middle Aged; Molecular Targeted Therapy; Risk Factors; Sex Factors; Signal Transduction; Smoking

Diagnosis of abdominal aortic aneurysm (AAA) at preoperative stage is increasingly frequent. It carries both a local risk of rupture and an increased global cardiovascular risk. Patients with AAA have indeed a 20 times higher risk of dying from myocardial infarction or stroke than from a ruptured aneurysm. Cardiovascular risk factors control is therefore essential, particularly smoking cessation. Treatment in cardiovascular prevention is also warranted. Seeking for atheromatous sites is needed as they determine prognosis. Evidence of the benefit of medical treatment to slow AAA growth is still lacking. In practice, it is recommended to prescribe statins and angiotensin converting enzyme inhibitor to prevent cardiovascular events. These preventive measures are as well necessary to improve postoperative prognosis and must be continued after surgical repair. A vascular medical and surgical cooperation is primordial to enhance comprehensive management of patients with AAA.

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Aortic Aneurysm, Abdominal; Aortic Rupture; Calibration; Cardiovascular Agents; Disease Progression; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors

This review describes ongoing efforts to develop a medical therapy to limit abdominal aortic aneurysm (AAA) growth.. Data from animal model studies, human investigations, and clinical trials are described.. Studies in rodent models and human samples have suggested a number of potential targets for slowing or halting AAA growth. A number of clinical trials are now examining the value of medications targeting some of the pathways identified. These trials have a number of challenges, including identifying medications safe to use in older patients with multiple comorbidities, developing accurate outcome assessments, and minimizing the dropout of patients during the trials. Three recent trials have reported no benefit of the antibiotic doxycycline, a mast cell inhibitor, an angiotensin-converting enzyme inhibitor, or a calcium channel blocker in limiting AAA growth. A number of other trials examining angiotensin receptor blockers, cyclosporine, and an antiplatelet agent are currently underway.. Further refinement of drug discovery pathways and testing paradigms are likely needed to develop effective nonsurgical therapies for AAA.

Topics: Animals; Aorta, Abdominal; Aortic Aneurysm, Abdominal; Cardiovascular Agents; Dilatation, Pathologic; Disease Progression; Drug Discovery; Humans

Pharmacological prophylaxis has been proven to reduce the risk of cardiovascular events in individuals with atherosclerotic occlusive arterial disease. However, the role of prophylaxis in individuals with abdominal aortic aneurysm (AAA) remains unclear. Several studies have shown that despite successful repair, those people with AAA have a poorer rate of survival than healthy controls. People with AAA have an increased prevalence of coronary heart disease and risk of cardiovascular events. Despite this association, little is known about the effectiveness of pharmacological prophylaxis in reducing cardiovascular risk in people with AAA. This is an update of a Cochrane review first published in 2014.. To determine the long-term effectiveness of antiplatelet, antihypertensive or lipid-lowering medication in reducing mortality and cardiovascular events in people with abdominal aortic aneurysm (AAA).. For this update the Cochrane Vascular Information Specialist (CIS) searched the Cochrane Vascular Specialised Register (14 April 2016). In addition, the CIS searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2016, Issue 3) and trials registries (14 April 2016) and We also searched the reference lists of relevant articles.. Randomised controlled trials in which people with AAA were randomly allocated to one prophylactic treatment versus another, a different regimen of the same treatment, a placebo, or no treatment were eligible for inclusion in this review. Primary outcomes included all-cause mortality and cardiovascular mortality.. Two review authors independently selected studies for inclusion, and completed quality assessment and data extraction. We resolved any disagreements by discussion. Only one study met the inclusion criteria of the review, therefore we were unable to perform meta-analysis.. No new studies met the inclusion criteria for this update. We included one randomised controlled trial in the review. A subgroup of 227 participants with AAA received either metoprolol (N = 111) or placebo (N = 116). There was no clear evidence that metoprolol reduced all-cause mortality (odds ratio (OR) 0.17, 95% confidence interval (CI) 0.02 to 1.41), cardiovascular death (OR 0.20, 95% CI 0.02 to 1.76), AAA-related death (OR 1.05, 95% CI 0.06 to 16.92) or increased nonfatal cardiovascular events (OR 1.44, 95% CI 0.58 to 3.57) 30 days postoperatively. Furthermore, at six months postoperatively, estimated effects were compatible with benefit and harm for all-cause mortality (OR 0.71, 95% CI 0.26 to 1.95), cardiovascular death (OR 0.73, 95% CI 0.23 to 2.39) and nonfatal cardiovascular events (OR 1.41, 95% CI 0.59 to 3.35). Adverse drug effects were reported for the whole study population and were not available for the subgroup of participants with AAA. We considered the study to be at a generally low risk of bias. We downgraded the quality of the evidence for all outcomes to low. We downgraded the quality of evidence for imprecision as only one study with a small number of participants was available, the number of events was small and the result was consistent with benefit and harm.. Due to the limited number of included trials, there is insufficient evidence to draw any conclusions about the effectiveness of cardiovascular prophylaxis in reducing mortality and cardiovascular events in people with AAA. Further good-quality randomised controlled trials that examine many types of prophylaxis with long-term follow-up are required before firm conclusions can be made.

Topics: Antihypertensive Agents; Aortic Aneurysm, Abdominal; Cardiovascular Agents; Cardiovascular Diseases; Cause of Death; Humans; Metoprolol; Randomized Controlled Trials as Topic; Risk Factors

Abdominal aortic aneurysm refers to abdominal aortic dilation of 3.0 cm or greater. The main risk factors are age older than 65 years, male sex, and smoking history. Other risk factors include a family history of abdominal aortic aneurysm, coronary artery disease, hypertension, peripheral artery disease, and previous myocardial infarction. Diagnosis may be made by physical examination, an incidental finding on imaging, or ultrasonography. The U.S. Preventive Services Task Force released updated recommendations for abdominal aortic aneurysm screening in 2014. Men 65 to 75 years of age with a history of smoking should undergo one-time screening with ultrasonography based on evidence that screening will improve abdominal aortic aneurysm-related mortality in this population. Men in this age group without a history of smoking may benefit if they have other risk factors (e.g., family history of abdominal aortic aneurysm, other vascular aneurysms, coronary artery disease). There is inconclusive evidence to recommend screening for abdominal aortic aneurysm in women 65 to 75 years of age with a smoking history. Women without a smoking history should not undergo screening because the harms likely outweigh the benefits. Persons who have a stable abdominal aortic aneurysm should undergo regular surveillance or operative intervention depending on aneurysm size. Surgical intervention by open or endovascular repair is the primary option and is typically reserved for aneurysms 5.5 cm in diameter or greater. There are limited options for medical treatment beyond risk factor modification. Ruptured abdominal aortic aneurysm is a medical emergency presenting with hypotension, shooting abdominal or back pain, and a pulsatile abdominal mass. It is associated with high prehospitalization mortality. Emergent surgical intervention is indicated for a rupture but has a high operative mortality rate.

Topics: Age Distribution; Aged; Aged, 80 and over; Aneurysm, Ruptured; Aortic Aneurysm, Abdominal; Cardiovascular Agents; Cardiovascular Diseases; Diagnostic Imaging; Female; Humans; Male; Mass Screening; Obesity; Practice Guidelines as Topic; Risk Factors; Sex Distribution; Smoking; Vascular Surgical Procedures

Management of abdominal aortic aneurysms (AAAs) relies on surgical repair of larger AAAs. Consequently medical interventions inhibiting AAA progression could greatly reduce the need for surgical repair. A spectrum of pharmaceutical strategies has been reported, albeit conclusions often appear contradictory. Given the longstanding interest in pharmaceutical AAA stabilization, a systematic review of the available literature is relevant.. The aim is to provide an up to date systematic review of the available data on pharmaceutical therapies for stabilizing or impeding AAA growth.. A search using Pubmed, Embase, Web of science, Cochrane, CINAHL, Academic Search Premier, and Science Direct identified 27 eligible papers that studied the clinical effect of the pharmaceutical therapy on AAA diameter growth.. This review shows that there is currently no pharmaceutical strategy that reduces AAA growth. Most studies are of poor methodological quality. Initial promising reports are often not confirmed in subsequent larger studies, raising the possibility of selective reporting.. There is currently no pharmaceutical means that halts AAA growth.

Topics: Aortic Aneurysm, Abdominal; Aortic Rupture; Cardiovascular Agents; Disease Progression; Humans; Risk Assessment; Risk Factors; Treatment Outcome

Pharmacological prophylaxis has been proven to reduce the risk of cardiovascular events in patients with atherosclerotic occlusive arterial disease. However, the role of prophylaxis in patients with abdominal aortic aneurysm (AAA) remains unclear. Several studies have shown that despite successful repair, those with AAA have a poorer rate of survival than healthy controls. People with AAA have an increased prevalence of coronary heart disease and risk of cardiovascular events. Despite this association, little is known about the effectiveness of pharmacological prophylaxis in reducing cardiovascular risk in people with AAA.. To determine the long-term effectiveness of antiplatelet, antihypertensive or lipid-lowering medication in reducing mortality and cardiovascular events in people with abdominal aortic aneurysm (AAA).. The Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (last searched April 2013) and CENTRAL (2013, Issue 3). Reference lists of relevant articles were also checked.. Randomised controlled trials in which people with AAA were randomly allocated to one prophylactic treatment versus another, a different regimen of the same treatment, a placebo, or no treatment were eligible for inclusion in this review. Primary outcomes included all-cause mortality and cardiovascular mortality.. Selection of the studies, quality assessment and data extraction were completed independently by two review authors. Any disagreements were resolved by discussion. Only one study was included in the review, therefore meta-analysis could not be performed.. One randomised controlled study was included in the review. A subgroup of 227 patients with AAA received either metoprolol (N = 111) or placebo (N = 116). There was no clear evidence that metoprolol reduced all-cause mortality (odds ratio (OR) 0.17, 95% confidence interval (CI) 0.02 to 1.41), cardiovascular death (OR 0.20, 95% CI 0.02 to 1.76), AAA-related death (OR 1.05, 95% CI 0.06 to 16.92) or increased nonfatal cardiovascular events (OR 1.44, 95% CI 0.58 to 3.57) 30 days postoperatively. Furthermore, at six months postoperatively, estimated effects were compatible with benefit and harm for all-cause mortality (OR 0.71, 95% CI 0.26 to 1.95), cardiovascular death (OR 0.73, 95% CI 0.23 to 2.39) and nonfatal cardiovascular events (OR 1.41, 95% CI 0.59 to 3.35). Adverse drug effects were reported for the whole study population and were not available for the subgroup of participants with AAA. The study was deemed to be at a generally low risk of bias.. Due to the limited number of trials, there is insufficient evidence to draw any conclusions about the effectiveness of cardiovascular prophylaxis in reducing mortality and cardiovascular events in people with AAA. Further good-quality randomised controlled trials examining many types of prophylaxis with long-term follow-up are required before firm conclusions can be made.

Topics: Antihypertensive Agents; Aortic Aneurysm, Abdominal; Cardiovascular Agents; Cardiovascular Diseases; Cause of Death; Humans; Metoprolol; Randomized Controlled Trials as Topic; Risk Factors

Abdominal aortic aneurysms (AAA) are the most common arterial aneurysms. Endovascular or open surgical aneurysm repair is indicated in patients with large AAA ≥ 5.5 cm in diameter as this prevents aneurysm rupture. The presence even of small AAAs not in need of immediate repair is associated with a very high cardiovascular risk including myocardial infarction, stroke or cardiovascular death. This risk by far exceeds the risk of aneurysm rupture. These patients therefore should be considered as high-risk patients and receive optimal medical treatment and life-style modification of their cardiovascular risk factors to improve their prognosis. In addition, these patients should be followed-up for aneurysm growth and receive medical treatment to decrease aneurym progression and rupture rate. Treatment with statins has been shown to reduce cardiovascular mortality in these patients, and also slows the rate of AAA growth. Use of beta-blockers, ACE inhibitors and AT1-receptor antagonists does not affect AAA growth but may be indicated for comorbidities. Antibiotic therapy with roxithromycin has a small effect on AAA growth, but this effect must be critically weighed against the potential risk of wide-spread use of antibiotics.. Bauchaortenaneurysmen (BAA) sind die häufigste Manifestation arterieller Aneurysmen. Eine endovaskuläre oder offene chirurgische Aneurysmaausschaltung ist bei großen BAA von ≥ 5,5 cm Durchmesser indiziert, da damit eine Ruptur verhindert werden kann. Kleine BAA ohne Indikation für sofortige chirurgische oder interventionelle Intervention sind assoziiert mit einem sehr hohen Risiko für kardiovaskuläre Ereignisse, wie Myokardinfarkt, Schlaganfall oder kardiovaskulärem Tod. Dieses Risiko überwiegt bei kleinem BAA das Risiko einer Ruptur bei Weitem. Diese Patienten müssen daher als Hochrisikopatienten betrachtet werden und sollen eine optimale medikamentöse Behandlung und Lebensstilmodifikation ihrer kardiovaskulären Risikofaktoren erhalten, um die Prognose zu verbessern. Zudem sollten diese Patienten überwacht werden bzgl. Wachstum des Aneurysmas und eine medikamentöse Therapie erhalten, welche das Aneurysmawachstum verzögert und die Rupturrate verringert. Eine Behandlung mit Statinen reduziert die kardiovaskuläre Mortalität dieser Patienten und verringert zudem das Wachstum von BAA. Betablocker, ACE Inhibitoren und AT1-Rezeptor Antagonisten haben keinen Einfluss auf die Wachstumsrate von BAA, können aber aufgrund von Komorbiditäten indiziert sein. Eine antibiotische Behandlung mit Roxithromycin hat einen geringen Effekt auf die Wachstumsrate von BAA. Dieser Effekt muss jedoch kritisch abgewogen werden gegen das potentielle Risiko eines breiten Einsatzes von Antibiotika.

Topics: Anti-Bacterial Agents; Aortic Aneurysm, Abdominal; Aortic Rupture; Cardiovascular Agents; Humans; Patient Selection; Risk Assessment; Risk Factors; Risk Reduction Behavior; Time Factors; Treatment Outcome

Aortic aneurysms are a common finding in elderly patients. Rupture of an aortic aneurysm is a catastrophic event associated with a very high mortality.. To review the current literature on aortic aneurysmal disease, including the recommended referral threshold, surveillance guidelines and treatment options.. Screening of men aged 65 years and over has been shown to reduce aneurysm related mortality, however, no formal screening guidelines exist in Australia. In addition to the risk of aneurysm expansion and rupture, patients are at increased risk of cardiovascular morbidity and mortality. Small aneurysms should be managed with surveillance and cardiovascular risk factor modification. Large aneurysms should be referred promptly to a vascular surgeon for assessment and repair. Symptomatic and ruptured aneurysms require emergency assessment and treatment. Advances in endovascular techniques enable most patients with aortic aneurysms to be treated with minimally invasive stent grafts, which have lower perioperative complication rates than open repair.

Topics: Aortic Aneurysm, Abdominal; Aortic Dissection; Aortic Rupture; Australia; Blood Vessel Prosthesis Implantation; Cardiovascular Agents; Combined Modality Therapy; Endovascular Procedures; Humans; Mass Screening; Population Surveillance; Practice Guidelines as Topic; Referral and Consultation; Risk Factors

Surveillance is a common management strategy for small abdominal aortic aneurysm (AAA) (3.0-5.4 cm in diameter). Individual characteristics, other than diameter, may influence aneurysm growth or rupture rates.. Individual data were collated from 15 475 people under follow-up for a small aneurysm in 18 studies. The influence of co-variables (including demographics, medical and drug history) on aneurysm growth and rupture rates (analysed using longitudinal random-effects modelling and survival analysis with adjustment for aneurysm diameter) were summarized in an individual patient meta-analysis.. The mean aneurysm growth rate of 2.21 mm/year was independent of age and sex. Growth rate was increased in smokers (by 0.35 mm/year) and decreased in patients with diabetes (by 0.51 mm/year). Mean arterial pressure had no effect and antihypertensive or other cardioprotective medications had only small, non-significant effects on aneurysm growth, consistent with the observation that calendar year of enrollment was not associated with growth rate. Rupture rates were almost fourfold higher in women than men (P < 0.001), were double in current smokers (P = 0.001) and increased with higher blood pressure (P = 0.001).. Follow-up schedules for individuals with a small AAA may need to consider diabetes and smoking, in addition to aneurysm diameter. The differing risk factors for growth and rupture suggest that a lower threshold for surgical intervention in women may be justified. No single drug used for cardiovascular risk reduction had a major effect on the growth or rupture of small aneurysms.

Topics: Aged; Aortic Aneurysm, Abdominal; Aortic Rupture; Cardiovascular Agents; Diabetes Mellitus; Female; Humans; Male; Prevalence; Risk Factors; Smoking

Multiple medical therapies have been proposed to prevent abdominal aortic aneurysm expansion. Use of these medications, hormones, vitamins, and dietary products is based on their ability to alter the pathophysiology of continued aortic wall growth. In this review, the explanation of how these medications can achieve suppression of abdominal aortic aneurysm is explained in relation to their effect on the various aspects of aortic wall inflammation. Despite the large number of animal and observational studies, there remain very few randomized clinical trials to support use of any of these agents. However, there may be sufficient evidence to suggest that statins, doxycycline, vitamin E, cyclooxygenase-2 inhibitors, angiotensin-converting enzyme inhibitors, and angiotensin II receptor blockers can prove beneficial in some individuals.

Topics: Animals; Aortic Aneurysm, Abdominal; Cardiovascular Agents; Disease Progression; Humans; Treatment Outcome

Conventional open repair or endovascular aneurysm repair is indicated for infrarenal abdominal aortic aneurysm (AAA) when the diameter of the latter is ≥ 5.5 cm. This therapeutic strategy is based on results of randomized trials of open repair versus ultrasound surveillance of small AAA (<5.5 cm). Studies of screening for AAA have shown that >90% of aneurysms detected are small aneurysms (<5.5 cm). Despite the low annual risk of rupture of these aneurysms, patients with small AAA are left with a potentially life-threatening disease for which no immediate treatment is available. Hence, medical treatment directed at limiting the expansion of small AAA has emerged as an alternative therapeutic strategy. Randomized trials of doxycycline, roxithromycin, and propranolol in patients with small AAA have been published. The results of the doxycycline and roxithromycin trials suggest that both medications can limit AAA expansion, especially during the first year of treatment. Propranolol did not limit AAA expansion, and the trials were stopped because of its serious side effects. In other studies, statins and indomethacin have also been shown to limit AAA expansion. However, these studies were observational with relatively small numbers of patients. Thus, large randomized controlled trials with long follow-up are needed to objectively assess the efficacy of medications that have shown potential in limiting AAA expansion. In addition, recent evidence of regression of AAA in experimental animal models is likely to change our concepts of the molecular pathogenesis of AAA, and could make medical treatment of small AAA a possibility.

Topics: Aortic Aneurysm, Abdominal; Cardiovascular Agents; Disease Progression; Doxycycline; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Indomethacin; Propranolol; Risk Factors; Risk Reduction Behavior; Roxithromycin; Time Factors; Treatment Outcome

Abdominal aortic aneurysms (AAA) affect 5% of the population in developed countries and are characterized by progressive aortic dilatation with an unpredictable time course. This condition is more common in men than in women, and in smokers than in nonsmokers. If left untreated, AAA can result in aortic rupture and death. Pathologically, aortic extracellular matrix degradation, inflammation, and neovascularization are hallmarks of AAA. Diagnosis of AAA and subsequent surveillance utilize established aortic imaging methods, such as ultrasound, CT, and MRI. More-speculative diagnostic approaches include molecular and cellular imaging methods that interrogate the underlying pathological processes at work within the aneurysm. In this Review, we explore the current diagnostic and therapeutic strategies for the management of AAA. We also describe the diagnostic potential of new imaging techniques and therapeutic potential of new treatments for the management of small AAA.

Topics: Aortic Aneurysm, Abdominal; Aortography; Cardiovascular Agents; Diagnostic Imaging; Endovascular Procedures; Humans; Predictive Value of Tests; Risk Factors; Treatment Outcome; Vascular Surgical Procedures

Statins possess several pleiotropic effects and have been shown in vitro and in vivo to inhibit the expression of inflammatory mediators and downregulate molecules involved in extracellular matrix (ECM) degradation. Recent observational studies in humans suggest that statins may have a role in abdominal aortic aneurysm (AAA) prevention or may even inhibit aneurysm expansion. In this review, we summarize the effects of statins on the vessel wall of aneurysmal aortas and currently available data concerning their inhibitory effects on aneurysm progression.

Topics: Animals; Aortic Aneurysm, Abdominal; Atorvastatin; Blood Vessels; Cardiovascular Agents; Disease Progression; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Inflammation; Matrix Metalloproteinases; Models, Animal; Pyrroles; Risk Assessment; Simvastatin

Abdominal aortic aneurysms (AAA) and coronary artery disease (CAD) have traditionally been regarded as two separate vessel disorders with a common background. Atherosclerosis has always been considered as the basic pathophysiologic process. However, during the last decade, evidence has emerged with differences between AAA and CAD. Firstly, data regarding the prevalence of AAA and CAD are different. Secondly, the risk profiles between AAA and CAD differ, mainly regarding gender, age and diabetes mellitus. Thirdly, despite the intensive treatment of CAD and improved outcome, the prevalence of AAA has not changed during the last decade. In this review we will discuss the characteristics of CAD in patients with AAA. In the first part we focus on epidemiological data of CAD in AAA patients. The pathophysiology of both AAA and CAD will be described in the second part. There is a common pathway between pathophysiology and risk profiles that is discussed in the third chapter. Based on the presence of risk factors and their influence on cardiovascular events, the preoperative work-up and testing for CAD in AAA has gained an important role. The role of (non)-invasive testing will be described in the fourth chapter. The treatment of AAA traditionally consisted solely of surgery. However, due to the influence of CAD on adverse outcomes, medical intervention is potentially useful. Surgical approaches for the treatment of both AAA and CAD, and most importantly, their influence on long-term outcome will be discussed in the fifth chapter.

Topics: Aged; Aortic Aneurysm, Abdominal; Cardiovascular Agents; Coronary Artery Bypass; Coronary Artery Disease; Female; Humans; Incidence; Male; Predictive Value of Tests; Prevalence; Risk Assessment; Risk Factors; Treatment Outcome; Vascular Surgical Procedures

Abdominal aortic aneurysm (AAA) is a common degenerative condition with high mortality in older men. Elective surgical or endovascular repair is performed to prevent rupture of large AAAs. In contrast, despite gradual expansion, small AAAs have a low risk of rupture, and there is currently no well-defined treatment strategy for them. Therefore, a pharmacological approach for AAA is expected in the clinical setting. Indeed, several therapeutic effects of pharmacological agents have been reported in experimental models, and some agents have undergone clinical trials. Treatment with statins, angiotensin-converting enzyme-inhibitors, antibiotics, and anti-inflammatory agents appears to inhibit the growth rate of AAA in humans. However, as the sample size and follow-up period were limited in these studies, a large randomized study with long-term follow-up of small AAA should be performed to clarify the effect of these agents. Recently, the regression of AAA using molecular pharmacological approaches was reported in experimental studies. The characteristics of these strategies are the regulation of multiple molecular mediators and the signalling networks associated with AAA formation. On the basis of the results of these investigations, it may be possible to repair the injured aortic wall and obtain the remission of AAA using pharmacological therapy.

Topics: Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Animals; Anti-Bacterial Agents; Aorta, Abdominal; Aortic Aneurysm, Abdominal; Cardiovascular Agents; Drugs, Investigational; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Remission Induction; Signal Transduction; Time Factors; Treatment Outcome

Abdominal aortic aneurysms (AAA) have a prevalence between 1.3-8.9% in men and 1.0-2.2% in women aged above 55 years. Furthermore, AAA cause 1-3% of all deaths among men aged 65-85 years in developed countries. As the disorder is invariably associated with severe atherosclerotic damage of the arterial wall, it has traditionally been regarded as a direct consequence of generalized atherosclerotic disease. In patients with occlusive aortic disease, dyslipidemia is a well established risk factor. However, in patients with aneursymatic aortic disease, the association between dyslipidemia and the development of AAA is less clear. Large clinical trials in patients with cardiac and peripheral arterial disease have shown the strong relation between dyslipidemia, statin therapy and the risk of cardiovascular disease. Importantly, the effects of statin therapy were still present irrespective of the decrease in serum cholesterol levels. These findings resulted in the discussion of potential non-lipid lowering effects of statin therapy. These ''pleiotropic effects'' compose a diversity of cellular events which have an effect on several components of the arterial wall, including: 1) endothelial cells; 2) smooth muscle cells; 3) platelets; 4) monocytes/macrophages; and 5) the process of inflammation. In the general population the role of dyslipidemia as an independent risk factor for AAA is debated. However, as patients with AAA frequently have concomitant arterial disease, statin therapy is often recommended. As a result, the non-lipid lowering effects of statins on aneurysm expansion rate are hardly studied, and most evidence comes from experimental and animal studies. In the current review article we provide an overview of all available literature on the effects of dyslipidemia, statin therapy and the risk of AAA expansion and rupture. In the first part we summarize all population-based studies that investigated the relation between hypercholesterolemia and the development of AAA. In the second part, the available literature regarding the effects of statins on aneurysm growth, expansion rate and the risk of rupture is summarized, including in vitro, animal and clinical human studies.

Topics: Aged; Aged, 80 and over; Animals; Aortic Aneurysm, Abdominal; Aortic Rupture; Cardiovascular Agents; Disease Models, Animal; Disease Progression; Dyslipidemias; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Middle Aged; Risk Assessment; Risk Factors; Treatment Outcome

Endovascular (EVAR) abdominal aortic aneurysm (AAA) repair has been established as a successful procedure in the short term and may constitute a viable long-term alternative to open repair (OR). The procedure has been associated with lower operative and mid-term morbidity and mortality compared to OR, but long-term results remain largely controversial. EVAR has also been associated with a significant risk of implant and procedure-related complications, such as graft thrombosis and cardiovascular events, necessitating interventional and pharmaceutical management. Medical management of patients undergoing EVAR is required for several different reasons. Patients with an AAA have an increased risk of cardiovascular death, necessitating treatment to reduce the overall risk for cardiovascular events. Treatment is in-line with the medical management of coronary artery disease including anti-platelet therapy and statins. Anti-platelet therapy is also mandatory to prevent complications such as graft-limb thrombosis and peripheral arterial disease (PAD), which is common in patients with an AAA. Especially in patients with PAD, aspirin, clopidogrel and statins remain the mainstay of medical management. Unfortunately, there is a lack of prospective randomised trials concerning the medical management of patients that have undergone abdominal aortic endo-grafting. We review the current literature on the medical treatment of patients undergoing EVAR, focusing on peri-operative management, anti-platelet agents and statins.

Topics: Aortic Aneurysm, Abdominal; Blood Vessel Prosthesis Implantation; Cardiovascular Agents; Cardiovascular Diseases; Combined Modality Therapy; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Platelet Aggregation Inhibitors; Postoperative Care; Preoperative Care; Treatment Outcome

Abdominal aortic aneurysm (AAA) is a common and deadly problem. The aortic diameter increases in association with a complex remodeling process that includes changes in the structure and content of key proteins, elastin and collagen. As these changes occur, the tissue mechanical properties also change. The natural history of AAA is progressive enlargement to a point of mechanical tissue failure typically followed by death. Currently, the marker used to predict the risk of impending rupture is the largest transverse diameter. After reaching a diameter threshold of 5.5 cm the AAA needs to be surgically repaired. This criterion does not consider any patient-specific information or heterogeneity of the AAA that may, in some cases, lead to rupture before the AAA reaches the standard intervention threshold. Conversely, in many patients, continued observation beyond this threshold is safe. While no medical treatment is yet approved, doxycycline (Doxy) has been shown to greatly reduce AAA growth in animal models and has been shown to slow growth in 1 small clinical trial. While larger prospective randomized trials are needed, one unknown is what effect Doxy has on the structural integrity of the aortic wall. That is, does slowed AAA growth, by Doxy treatment, prevent rupture, or does the wall continue to weaken and the AAA instead ruptures at a smaller diameter? Using an established animal model of AAA, we begun to determine the changes in tissue mechanics compliance of the aorta as the AAA develops. Our current research is focused on verifying that these changes mimic the observed changes seen in the human population as reported by other researchers, so that we can confidently study how potential drug therapies may affect wall strength and compliance in the human population. The long-term objectives are to understand better factors related to progression of AAA and help verify that drug therapy with Doxy will decrease the chance of rupture by preventing wall weakening and maintaining function of the aorta.

Topics: Animals; Aorta; Aortic Aneurysm, Abdominal; Aortic Rupture; Biomedical Research; Cardiovascular Agents; Compliance; Disease Progression; Doxycycline; Humans; Mass Screening; Mice; Models, Animal; Models, Cardiovascular; Patient Selection; Treatment Outcome; Vascular Surgical Procedures

Medical management of patients with abdominal aortic aneurysm (AAA) is required for several different reasons. Since these patients have an increased risk of cardiovascular death therapy to reduce cardiovascular events is essential. Treatment is in line with the medical management of coronary artery disease including smoking cessation, statins and anti-platelet therapy. Some of these therapies also will slow aneurysm growth. Currently there is no proven focused therapy that reduces aneurysm growth, but the emerging strategies are discussed. Medical management also is required to reduce peri-operative risks and stabilise endovascular aneurysm repair. Whilst some of the therapies targeting cardiovascular risk reduction may be helpful, other emerging strategies are discussed.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Animals; Anti-Bacterial Agents; Aortic Aneurysm, Abdominal; Aortic Rupture; Cardiovascular Agents; Cardiovascular Diseases; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Matrix Metalloproteinase Inhibitors; Perioperative Care; Practice Guidelines as Topic; Protease Inhibitors; Randomized Controlled Trials as Topic; Risk Assessment; Risk Factors; Treatment Outcome; Vascular Surgical Procedures

Use of molecular tools to diagnose and treat aortic disease, in particular, aortic aneurysms and aortic dissections, is still in its infancy, with great advancements expected in the future. Currently under investigation are the genetic markers linked to aortic disease that may help to identify patients at risk for their development prior to clinical presentation. In addition, specific gene defects may be identified that can assist in the understanding of the basic mechanisms contributing to development of aortic disease. Biomarkers are under investigation that can be used to monitor the development, progression, and possible response to therapy for aortic aneurysms and acute aortic syndromes. Equally important, further investigations into the molecular mechanisms involved in aortic pathology will result in increased understanding of the disease etiology and will lead to development of alternate therapies for these diseases prior to their catastrophic development. With advances in molecular technology, the molecular diagnosis and treatment of aortic diseases will begin to expand at a rapid rate and provide unique, improved therapies.

Topics: Aortic Aneurysm, Abdominal; Aortic Aneurysm, Thoracic; Aortic Diseases; Aortic Dissection; Biomarkers; Cardiovascular Agents; Genetic Predisposition to Disease; Genetic Therapy; Humans; Molecular Diagnostic Techniques; Risk Factors; Signal Transduction; Syndrome

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Algorithms; Aneurysm; Aorta, Abdominal; Aortic Aneurysm, Abdominal; Aortic Rupture; Atherosclerosis; Cardiovascular Agents; Combined Modality Therapy; Comorbidity; Diagnostic Imaging; Evidence-Based Medicine; Female; Femoral Artery; Humans; Iliac Artery; Intestines; Ischemia; Leg; Male; Mesenteric Arteries; Middle Aged; Peripheral Vascular Diseases; Popliteal Artery; Prevalence; Randomized Controlled Trials as Topic; Renal Artery; Risk Factors; Risk Reduction Behavior; Treatment Outcome; Vascular Surgical Procedures

A total of 1446 participants, 65- to 74-year-old men diagnosed with abdominal aortic aneurysm (AAA), peripheral arterial disease (PAD) or high blood pressure (HB) in the Viborg Vascular (VIVA) screening trial, were consecutively included and randomised to a telephone counselling (TC) or no TC 3 months after being screened positive. Data from VIVA were linked to data from Danish registers from 2007 to 2016. The primary outcome was a composite outcome of proportion of days covered by statin, antithrombotic drugs and antihypertensive agents and for each specific drug class at 6-month follow-up. The same outcomes were assessed at 12 and 60 months and considered secondary outcomes. Outcome measures are reported as risk differences (RD). There were no differences between the groups in relation to the composite of all three drug classes over 6 months of follow-up, RD = 4.1 (95% CI: -1.0; 9.1). A significant increase in redeemed statin prescriptions was observed in the intervention group at 6 months, RD = 9.8% (CI 95%: 0.5; 19.0). There was no intervention effect observed after 12 and 60 months. TC 3 months after screening improved adherence to statin at 6-month follow-up, but had no effect on the composite treatment, statins, antithrombotic or antihypertensive treatment over 60 months of follow-up.

Topics: Aged; Antihypertensive Agents; Aortic Aneurysm, Abdominal; Cardiovascular Agents; Counseling; Denmark; Diagnostic Screening Programs; Drug Prescriptions; Fibrinolytic Agents; Health Knowledge, Attitudes, Practice; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypertension; Male; Medication Adherence; Peripheral Arterial Disease; Telephone; Time Factors; Treatment Outcome

Matrix metalloproteinase-9 (MMP-9) is thought to play a central role in abdominal aortic aneurysm (AAA) initiation. Doxycycline, a tetracycline analogue, has direct MMP-9-inhibiting properties in vitro, and it effectively suppresses AAA development in rodents. Observed inhibition of AAA progression, and contradictory findings in human studies evaluating the effect of doxycycline therapy on aortic wall MMP-9, suggest that the effects of doxycycline extend beyond MMP-9 inhibition and that the effect may be dose-dependent.. This clinical trial evaluated the effect of 2 weeks of low- (50 mg/d), medium- (100 mg/d), or high-dose (300 mg/d) doxycycline vs no medication in four groups of 15 patients undergoing elective AAA repair. The effect of doxycycline treatment on MMP and cysteine proteases, and their respective inhibitors, was evaluated by quantitative polymerase chain reaction, Western blot analysis, immunocapture protease activity assays, and immunohistochemistry.. Doxycycline was well tolerated and no participants dropped out. Doxycycline treatment reduced aortic wall MMP-3 and MMP-25 messenger RNA expression (P < .045 and P < .014, respectively), selectively suppressed neutrophil collagenase and gelatinase (MMP-8 and MMP-9) protein levels (P < .013 and <.004, respectively), and increased protein levels of the protease inhibitors tissue inhibitor of metalloproteinase 1 and cystatin C (P < .029). As for the apparent selective effect on neutrophil-associated proteases, we sought for a reducing effect on aortic wall neutrophil content that was indeed confirmed by immunohistochemical analysis that revealed a 75% reduction in aneurysm wall neutrophil content (P < .001).. Independent of its dose, short-term preoperative doxycycline therapy improves the proteolytic balance in AAA, presumably through an effect on aortic wall neutrophil content. This study provides a rationale for doxycycline treatment in patients with an AAA as well as in other (vascular) conditions involving neutrophil influx such as Kawasaki disease and Behçet disease.

Topics: Aged; Aged, 80 and over; Aorta, Abdominal; Aortic Aneurysm, Abdominal; Cardiovascular Agents; Cystatin C; Cysteine Endopeptidases; Dose-Response Relationship, Drug; Doxycycline; Female; Gene Expression Regulation, Enzymologic; Humans; Male; Matrix Metalloproteinase Inhibitors; Matrix Metalloproteinases; Middle Aged; Neutrophil Infiltration; Neutrophils; Prospective Studies; Protease Inhibitors; RNA, Messenger; Time Factors; Tissue Inhibitor of Metalloproteinase-1; Treatment Outcome; Vascular Surgical Procedures

To report the results of a trial comparing endovascular aneurysm repair (EVAR) to open repair (OR) and best medical therapy (BMT) involving high-risk patients with abdominal aortic aneurysms (AAA) suitable for EVAR.. From 2002 to 2007, 1083 patients with aortic aneurysm disease were referred to a tertiary care university hospital. Of these, 162 (119 men; mean age 76 years) were high-risk patients with AAAs anatomically suitable for EVAR. Following comprehensive consultation with the patient, the family, and the primary physician, elective treatment was selected: OR (n=52), EVAR (n=66), or BMT (n=44). Outcomes were compared using Kaplan-Meier survival analyses and a parameter that measured the quality time spent without symptoms of disease or toxicity of treatment (Q-TWIST).. Four-year freedom from aneurysm-related death following EVAR (96.7%) was markedly better compared to BMT (66.8%; p=0.002) and was similar to OR (93.9%, p=0.483). Four-year freedom from major adverse clinical events was significantly better with EVAR (78%) compared with BMT (28%; p=0.001) and was equivalent to OR (75%; p=0.519). The 4-year intervention-free survival rate for EVAR (95%) almost matched OR (98%; p=0.410). At 4 years, Q-TWIST was 3.64 years for EVAR patients, 3.60 years for OR, and 2.22 years for BMT. Q-TWIST significantly improved with EVAR compared to OR (p<0.003). In the cost analysis, 52 high-risk patients were treated with OR over the 5-year period (2002-2007) at a total inpatient cost of 1,257,457 euro. The 66 patients treated with EVAR (14 patients more than OR) incurred a lower cost of 1,129,138 euro. Including the cost of follow-up over 4 years, the mean cost per patient was 18,476 euro for EVAR and 24,252 euro for OR, a savings of 5,776 euro per patient treated with EVAR.. In high-risk patients, EVAR reduces aneurysm-related death compared to BMT. Equated to the gold standard of open repair, EVAR, as a "one-time procedure," substantially reduces operative morbidity, hospital stay, costs, and utilization of intensive care facilities if performed in a high-volume center.

Topics: Aged; Aortic Aneurysm, Abdominal; Blood Vessel Prosthesis Implantation; Cardiovascular Agents; Cost-Benefit Analysis; Feasibility Studies; Female; Health Care Costs; Humans; Ireland; Kaplan-Meier Estimate; Male; Minimally Invasive Surgical Procedures; Proportional Hazards Models; Prospective Studies; Quality of Life; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome

To describe index visits for acute aortic dissection (AD) to an academic center and validate the prevailing claims-based methodology to identify and stratify them.. Inpatient hospitalizations at a single center assigned an International Classification of Diseases, Ninth Revision (ICD-9) diagnosis code for AD from January 2005 to September 2015 were identified. Diagnoses were verified by review of medical records and imaging studies. All visits were secondarily stratified with the algorithm based on ICD-9 codes. Sensitivity and specificity analyses were conducted to evaluate the ability of the algorithm to correctly identify acute AD by Stanford class and treatment modality (type A open repair [TAOR], type B open repair [TBOR], thoracic endovascular repair [TEVAR], medical management [MM]).. In the study interval, there were 1245 visits coded for AD attributed to 968 unique patients. Chart review verification demonstrated that the majority of visits were for AD (79%; n = 981), of which 32% (n = 310) were for an index acute AD event. The true distribution of acute AD visit classifications was TAOR (46.1%; n = 143), TBOR (5.2%; n = 16), TEVAR (7.7%; n = 24), and MM (39.4%; n = 122). The algorithm, which used ICD-9 codes, identified 631 acute visits and stratified them as TAOR (27.1%; n = 171), TBOR (4.1%; n = 26), TEVAR (4.9%; n = 31), and MM (63.9%; n = 403). Analyses demonstrated high specificities, but generally low sensitivities of the algorithm (TAOR: sensitivity, 58%, specificity, 92%; TBOR: sensitivity, 13%, specificity, 98%; TEVAR: sensitivity, 17%, specificity, 98%; MM: sensitivity, 73%, specificity, 72%).. The prevalent claims-based strategy to identify hospitalizations with acute AD is specific, but lacks sensitivity. Caution should be exercised when studying AD with ICD-9 codes and improvements to existing claims-based methodologies are necessary to support future study of acute AD.

Topics: Administrative Claims, Healthcare; Aged; Algorithms; Aortic Aneurysm, Abdominal; Aortic Aneurysm, Thoracic; Aortic Dissection; Blood Vessel Prosthesis Implantation; Cardiovascular Agents; Data Mining; Databases, Factual; Endovascular Procedures; Female; Humans; International Classification of Diseases; Male; Middle Aged; Patient Admission; Reproducibility of Results; Retrospective Studies

Abdominal aortic aneurysm (AAA) remains the second most frequent vascular disease with high mortality but has no approved medical therapy. We investigated the direct role of apelin (APLN) in AAA and identified a unique approach to enhance APLN action as a therapeutic intervention for this disease. Loss of APLN potentiated angiotensin II (Ang II)-induced AAA formation, aortic rupture, and reduced survival. Formation of AAA was driven by increased smooth muscle cell (SMC) apoptosis and oxidative stress in

Topics: Aged; Aged, 80 and over; Angiotensin II; Angiotensin-Converting Enzyme 2; Animals; Aorta, Abdominal; Aortic Aneurysm, Abdominal; Apelin; Apoptosis; Cardiovascular Agents; Diet, High-Fat; Disease Models, Animal; Female; Gene Knockdown Techniques; Humans; Male; Mice, Transgenic; Middle Aged; Myocytes, Smooth Muscle; Neprilysin; Oxidative Stress; Peptidyl-Dipeptidase A; Phenylephrine; Primary Cell Culture; Proteolysis; Receptors, LDL; RNA, Small Interfering; Vascular Remodeling

Abdominal aortic aneurysm (AAA) is a vascular disease characterized by chronic inflammation in the infrarenal aorta. Epidemiologic data have clearly linked tobacco smoking to aneurysm formation and a faster rate of expansion. It suggested that nicotine, one of the main ingredients of tobacco, has been suggested to be associated with AAA development and rupture. In the condition where no established drugs are available; therefore, an effective approach to prevent the vascular damage from nicotine consumption may be the use of dietary functional food factors. However, little is known about the relationship between dietary components and AAA. In this study, we estimated the effect of dietary deoxyribonucleic acid (DNA) on the vascular wall. After habituation for 5 d, the mice were divided into four groups: control diet and distilled water group (C), DNA-Na diet and distilled water group (DNA), control diet and 0.5 mg/mL nicotine solution group (C-Nic), DNA-Na diet, and 0.5 mg/mL nicotine solution group (DNA-Nic). The dietary DNA attenuated the degradation of elastin fibers induced by nicotine administration. The areas stained positive for MMP-2 in the DNA-Nic group were significantly suppressed compared to C-Nic mice. These data suggest that the dietary DNA may prevent the weakening of the aortic wall via inhibition of the MMP-2-dependent pathway. In conclusion, we have revealed the protective effect of dietary DNA on the vascular pathology of nicotine-administrated mice. A nucleic acid-rich diet might be useful for people who consume nicotine via smoking, chewing tobacco, or nicotine patches.

Topics: Adventitia; Animals; Anti-Inflammatory Agents, Non-Steroidal; Antioxidants; Aorta, Abdominal; Aortic Aneurysm, Abdominal; Cardiovascular Agents; Dietary Supplements; Disease Models, Animal; DNA; Elastin; Endothelium, Vascular; Immunohistochemistry; Male; Matrix Metalloproteinase 2; Mice, Inbred C57BL; Nicotine; Oxidative Stress; Proteolysis

Abdominal aortic aneurysm (AAA) is a common aortic disease with a progressive nature. There is no approved pharmacological treatment to effectively slow aneurysm growth or prevent rupture. Necroptosis is a form of programmed necrosis that is regulated by receptor-interacting protein kinases (RIPs). We have recently demonstrated that the lack of RIP3 in mice prevented aneurysm formation. The goal of the current study is to test whether perturbing necroptosis affects progression of existing aneurysm using the RIP1 inhibitors Necrostatin-1 (Nec-1) and an optimized form of Nec-1, 7-Cl-O-Nec-1 (Nec-1s). Seven days after aneurysm induction by elastase perfusion, mice were randomly administered DMSO, Nec-1 (3.2 mg/kg/day) and Nec-1s (1.6 mg/kg/day) via intraperitoneal injection. Upon sacrifice on day 14 postaneurysm induction, the aortic expansion in the Nec-1s group (64.12 ± 4.80%) was significantly smaller than that of the DMSO group (172.80 ± 13.68%) (P < 0.05). The mean aortic diameter of Nec-1 treated mice appeared to be smaller (121.60 ± 10.40%) than the DMSO group, though the difference was not statistically significant (P = 0.1). Histologically, the aortic structure of Nec-1s-treated mice appeared normal, with continuous and organized elastin laminae and abundant αActin-expressing SMCs. Moreover, Nect-1s treatment diminished macrophage infiltration and MMP9 accumulation and increased aortic levels of tropoelastin and lysyl oxidase. Together, our data suggest that pharmacological inhibition of necroptosis with Nec-1s stabilizes pre-existing aneurysms by diminishing inflammation and promoting connective tissue repair.

Topics: Animals; Anti-Inflammatory Agents; Aortic Aneurysm, Abdominal; Apoptosis; Cardiovascular Agents; Cell Movement; Disease Models, Animal; Elastin; Gene Expression Regulation; GTPase-Activating Proteins; Humans; Imidazoles; Indoles; Injections, Intraperitoneal; Macrophages; Male; Matrix Metalloproteinase 9; Mice; Mice, Inbred C57BL; Myocytes, Smooth Muscle; Necrosis; Pancreatic Elastase; Protein-Lysine 6-Oxidase; Tropoelastin

Abdominal aortic aneurysm (AAA) is a potentially life-threatening condition associated with increased cardiovascular mortality. This study aims to evaluate effects of medical assessment prior to endovascular repair (EVAR) for AAA on long term survival and causes of death.. A retrospective study comparing patients treated with EVAR for AAA from 1998 to 2006, having undergone standardized preoperative work-up including spirometry and echocardiography (group 1, N.=304), to patients undergoing EVAR 2007 to 2011 after individual assessment by a vascular physician aiming to optimize cardiovascular medication and reveal previously unknown illnesses (group 2, N.=201). Median follow-up was 84 months (Inter Quartile Range [IQR] 40-84) in group 1, and 60 months (IQR 45-75) in group 2.. The use of lipid lowering agents (92%; P<0.001), anti-platelet (85%; P<0.001), antihypertensive drugs (94%; P<0.001), and beta receptor blockers (78%; P<0.001) was higher in group 2. In multivariable analysis adjusting for AAA-size ≥6.0 cm, signs of ischemia on ECG, and chronic kidney disease stage ≥3, group 1 had significantly higher both 1-year (OR 3.2 [95% CI 1.2-9.0]) and 2-year mortality (OR 2.3 [95% CI 1.2-4.6]), whereas no differences were found between groups in survival beyond 2 years. Vascular disease was the most common cause of death in both groups (62% and 55%; P=0.29).. Individualized preoperative evaluation by a vascular physician prior to elective EVAR was associated with reduced 1- and 2-year mortality, presumably related to more effective pharmacological cardiovascular prevention.

Topics: Aged; Aged, 80 and over; Aortic Aneurysm, Abdominal; Blood Vessel Prosthesis Implantation; Cardiovascular Agents; Echocardiography; Elective Surgical Procedures; Electrocardiography; Endovascular Procedures; Female; Humans; Kaplan-Meier Estimate; Logistic Models; Male; Multivariate Analysis; Odds Ratio; Physician's Role; Predictive Value of Tests; Proportional Hazards Models; Registries; Retrospective Studies; Risk Factors; Spirometry; Time Factors; Treatment Outcome

Cardiovascular complications, such as death, myocardial infarction, or heart failure, are the leading causes of morbidity and mortality in adult patients undergoing major noncardiac surgery.. To evaluate the effects of an accurate preoperative cardiac evaluation, together with optimized perioperative drug therapy, in reducing cardiovascular events in patients undergoing open aortic surgery for abdominal aneurysm.. Between January 2000 and December 2008, we considered all consecutive patients undergoing elective abdominal aortic open surgery at the Vascular Surgery Unit of the University of Study-Spedali Civili (Italy). Since January 2003, we have used an intensive cardiac preoperative evaluation: patients with at least one cardiac risk factor received a preoperative cardiac evaluation; all non-invasive and invasive tests were performed preoperatively when indicated by the consultant cardiologist, that also optimized the pharmacological perioperative therapy. The outcome of the 418 patients undergoing surgery between 2003 and 2008 was compared with those of the 204 patients in the previous triennium 2000 to 2002, when only patients with positive history for cardiac disease received a standard preoperative cardiological clinical or instrumental evaluation.. Patients enrolled in the 2003 to 2008 interval were slightly older and with a higher prevalence of comorbidities compared with those observed in the previous triennium; furthermore, the number of noninvasive tests performed before surgery increased significantly. Nevertheless, the number of major cardiac perioperative complications decreased over time: particularly, in-hospital mortality rate was 0.9% in the latter period, compared with 3.4% in the years 2000 to 2002. Also, the long-term mortality was significantly reduced in patients operated on between 2003 and 2008 compared with those operated on in the previous triennium.. These data suggest a significant benefit of an intensive cardiac preoperative evaluation in reducing the incidence of perioperative and postoperative cardiac morbidity and mortality.

Topics: Adult; Aged; Aged, 80 and over; Aortic Aneurysm, Abdominal; Cardiovascular Agents; Cardiovascular Diseases; Chi-Square Distribution; Comorbidity; Elective Surgical Procedures; Female; Heart Function Tests; Humans; Italy; Male; Middle Aged; Predictive Value of Tests; Preoperative Care; Retrospective Studies; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome; Vascular Surgical Procedures

The aim of this study was to compare preoperative patient evaluation by a vascular physician with a standardized workup protocol prior to elective endovascular aneurysm repair (EVAR) for abdominal aortic aneurysm (AAA), in terms of differences in patient medication and mortality.. Consecutive patients with infrarenal AAA treated with standard EVAR from 1998 to 2006 (group 2) and 2007 to 2011 (group 1) were compared. Patients in group 1 (N.=201) were investigated preoperatively by a vascular physician, evaluating comorbidities and medication. Patients in group 2 (N.=304) underwent a standardized preoperative work-up including spirometry and echocardiography. Median time of follow-up was 23 months in group 1 and 71 months in group 2.. The proportion of patients who had on-going medication with anti-platelet and lipid lowering medication at admission was higher in group 1 compared to group 2 (62% versus 51%; P=0.013 and 68% versus 35%; P<0.001). In group 1, the proportion of newly instituted or increased dosage of anti-hypertensive, anti-platelet or lipid lowering medication at preoperative evaluation was 40%, 24% and 31%, respectively. The total cost for preoperative assessment per patient was 272 € in group 1 and 293 € in group 2 (P<0.001). There was no difference in 30-day (P=0.29) or long-term (P=0.24) mortality between the two groups.. Preoperative assessment by a vascular physician resulted in lower costs and improvement of medication against atherosclerosis, uncontrolled hypertension and perioperative ischemic cardiac events, but mortality was unaffected.

Topics: Aged; Aged, 80 and over; Aortic Aneurysm, Abdominal; Blood Vessel Prosthesis Implantation; Cardiovascular Agents; Chi-Square Distribution; Comorbidity; Diagnostic Techniques and Procedures; Echocardiography; Elective Surgical Procedures; Electrocardiography; Endovascular Procedures; Female; Hospital Costs; Humans; Kaplan-Meier Estimate; Kidney Function Tests; Male; Postoperative Complications; Predictive Value of Tests; Preoperative Care; Risk Assessment; Risk Factors; Spirometry; Sweden; Time Factors; Treatment Outcome

We investigated the effects of a biodegradable gelatin hydrogel sponge sheet (GHSS) or GHSS incorporating basic fibroblast growth factor (GHSS + bFGF), which could prolong the effects of bFGF, on the progression of experimental abdominal aortic aneurysms (AAAs). Experimental AAAs were induced in male Sprague-Dawley rats by intra-aortic elastase infusion. The rats were divided according to the following treatments: (1) untreated, (2) GHSS alone, (3) GHSS incorporating 100 ng, 1 microg, and 10 microg of bFGF. GHSSs were placed over the elastase-infused aortas. After 14 days, the GHSS alone group and the three groups with GHSS + bFGF demonstrated significantly smaller aortic diameters than the untreated group, and these groups significantly attenuated a reduction of the elastic fibers and smooth muscle cells in the pathological findings. However, no additional therapeutic effect was noted between the GHSS alone and GHSS + bFGF groups. Immunohistochemical analysis revealed an increase of positive cells for endogenous bFGF in the media and adventitia of both the GHSS alone and GHSS + bFGF groups in comparison to the untreated group. In conclusion, GHSS itself possessed significant therapeutic effects on AAA progression by inducing the production of endogenous bFGF, leading to the preservation of elastic fibers and smooth muscle cells.

Topics: Animals; Aorta; Aortic Aneurysm, Abdominal; Cardiovascular Agents; Delayed-Action Preparations; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Carriers; Fibroblast Growth Factor 2; Gelatin Sponge, Absorbable; Humans; Hydrogels; Male; Pancreatic Elastase; Rats; Rats, Sprague-Dawley; Recombinant Proteins; Time Factors

Patients with unrepaired abdominal aortic aneurysm (AAA) may have depression and other psychiatric disorders for which electroconvulsive therapy (ECT) may be recommended. It is unclear whether ECT, which transiently, yet markedly, increases blood pressure and heart rate, can be safely performed in patients with AAA. We investigated the safety of ECT in patients with unrepaired AAA.. A retrospective review was conducted of the medical records of all patients with unrepaired AAA who underwent ECT for severe depressive syndromes at Mayo Clinic, Rochester, Minn, between January 1, 1995, and June 30, 2007.. Eight patients (5 men and 3 women) with unrepaired AAA who underwent ECT were identified. Median age was 78.5 years (range, 67-83 years). All patients had AAA (median diameter, 3.95 cm [range, 3.0-5.2 cm]). The median number of treatments was 8.5 (range, 4-48). None of the patients died during the periprocedural period or experienced symptoms or signs suggestive of AAA expansion or rupture. Follow-up imaging data were available for 6 patients whose median post-ECT AAA diameter was 4.65 cm (range, 3.3-5.3 cm). Expansion of AAA ranged from 0.1 cm (for 11 and 13 months in 2 patients) to 1.0 cm (for 29 months in 1 patient), which is less than the expected mean expansion rates for AAAs of these diameters.. Electroconvulsive therapy was safe for 8 patients with unrepaired AAA treated at our institution. Our findings may be informative to clinicians who manage the care of patients with unrepaired AAA who are undergoing ECT.

Topics: Aged; Aged, 80 and over; Anesthesia; Aortic Aneurysm, Abdominal; Blood Pressure; Cardiovascular Agents; Depressive Disorder; Electroconvulsive Therapy; Female; Heart Rate; Humans; Male; Retrospective Studies; Safety; Seizures

Topics: Albuminuria; Aortic Aneurysm, Abdominal; Biomarkers; Cardiovascular Agents; Elective Surgical Procedures; Glomerular Filtration Rate; Humans; Ischemic Preconditioning; Kidney Diseases; Lower Extremity; Minimally Invasive Surgical Procedures; Myocardial Reperfusion Injury; Reperfusion Injury; Time Factors; Tourniquets; Treatment Outcome; Vascular Surgical Procedures

An imbalance in matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) are implicated in AAA formation. 3-Hydroxy-3-methylglutaryl coenzyme-A reductase inhibitors (statins) are known to reduce MMP levels. The aim of this study was to investigate the in vivo effect of statins on MMP levels in AAA.. Infra-renal aortic biopsies were obtained from the anterior sac of 63 patients undergoing asymptomatic repair. Seventeen patients were taking a statin pre-operatively, while 46 were not. The concentrations of MMP-1, -2, -3, -8, -9, -13, TIMP-1 and TIMP-2 were quantified using ELISA.. There was no difference in the concentration of MMP-1, -2, -8, -13, TIMP-1 or -2 in patients taking versus not taking a statin pre-operatively. In contrast levels of MMP-9 and MMP-3 were significantly lower in patients taking a statin.. These data demonstrate that statins decrease MMP-9 and MMP-3 levels and represent a potential pharmacotherapy in established AAA.

Topics: Aged; Aorta, Abdominal; Aortic Aneurysm, Abdominal; Blood Vessel Prosthesis Implantation; Cardiovascular Agents; Cohort Studies; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Matrix Metalloproteinase 3; Matrix Metalloproteinase 9

Topics: Animals; Aortic Aneurysm, Abdominal; Cardiovascular Agents; Disease Progression; Doxycycline; Enzyme Inhibitors; Male; Metalloendopeptidases; Pancreatic Elastase; Rats; Rats, Wistar; Tetracyclines