RESUMO
BACKGROUND: People with HIV (PWH) have an increased risk of cardiovascular disease. Previous cross-sectional data suggest there is a higher prevalence of abdominal aortic aneurysm (AAA) in PWH than in those without HIV. Whether PWH have an increased risk of incident AAA compared with those without HIV is unknown. METHODS: We analyzed data among participants without prevalent AAA from the Veterans Aging Cohort Study, a prospective, observational, longitudinal cohort of veterans with HIV matched 1:2 with veterans without HIV infection. We calculated AAA rates by HIV status and assessed the association between HIV infection and incident AAA using Cox proportional hazards models. We defined AAA using the International Classification of Diseases, 9th or 10th revision, or Current Procedural Terminology codes and adjusted all models for demographic characteristics, cardiovascular disease risk factors, and substance use. Secondary analyses examined the association between time-varying CD4+ T-cell count or HIV viral load and incident AAA. RESULTS: Among 143 001 participants (43 766 with HIV), over a median follow-up of 8.7 years, there were 2431 incident AAA events (26.4% among PWH). Rates of incident AAA per 1000 person-years were similar among PWH (2.0 [95% CI, 1.9-2.2]) and people without HIV (2.2 [95% CI, 2.1-2.3]). There was no evidence that HIV infection increased the risk of incident AAA compared with no HIV infection (adjusted hazard ratio, 1.02 [95% CI, 0.92-1.13]). In adjusted analyses with time-varying CD4+ T-cell counts or HIV viral load, PWH with CD4+ T-cell counts <200 cells/mm3 (adjusted hazard ratio, 1.29 [95% CI, 1.02-1.65]) or HIV viral load ≥500 copies/mL (adjusted hazard ratio, 1.29 [95% CI, 1.09-1.52]) had an increased risk of AAA compared with those without HIV. CONCLUSIONS: HIV infection is associated with an increased risk of AAA among those with low CD4+ T-cell counts or elevated HIV viral load over time.
Assuntos
Aneurisma da Aorta Abdominal , Doenças Cardiovasculares , Infecções por HIV , Veteranos , Humanos , Estudos de Coortes , Fatores de Risco , Doenças Cardiovasculares/epidemiologia , Estudos Prospectivos , Estudos Transversais , Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia , Aneurisma da Aorta Abdominal/epidemiologiaRESUMO
BACKGROUND: National survey data exploring the patient experience with lipedema are lacking. METHODS: We conducted national surveys from 2016 to 2022 of women with lipedema as well as female controls. Surveys collected information on symptomatology, pain, and therapies. We performed logistic regression comparing symptoms among those with lipedema versus controls adjusting for age and BMI. RESULTS: A total of 707 women with lipedema and 216 controls completed the surveys. Those with lipedema had a mean age of 48.6 years and mean BMI of 40.9 kg/m2. Lipedema symptom onset occurred frequently at puberty (48.0%) or pregnancy (41.2%). Compared to controls, women with lipedema were more likely to report leg swelling in heat (odds ratio [OR], 66.82; 95% CI, 33.04-135.12; p < 0.0001), easy bruising (OR, 26.23; 95% CI, 15.58-44.17; p < 0.0001), altered gait (OR, 15.54; 95% CI, 7.58-31.96; p < 0.0001), flu-like symptoms (OR, 12.99; 95% CI, 4.27-39.49; p < 0.0001), joint hypermobility (OR, 12.88; 95% CI, 6.68-24.81; p < 0.0001), cool skin (OR, 12.21; 95% CI, 5.20-28.69; p < 0.0001), varicose veins (OR, 11.29; 95% CI, 6.71-18.99; p < 0.0001), and fatigue (OR, 9.59; 95% CI, 6.10-15.09; p < 0.0001). Additionally, 70.3% had upper arm involvement, 21.2% reported foot swelling, and 16.6% reported foot pain. Most (52.2%) reported no symptom improvement with diet or exercise. Common therapies used included compression therapy (45.0%), gastric bypass (15.7%), and lower-extremity liposuction (14.0%). CONCLUSION: In a large, national, symptom survey, women with lipedema reported excess pain, swelling, and fat in the legs along with numerous symptoms beyond those classically described. Symptom responses to common therapies remain understudied.
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Lipedema , Gravidez , Feminino , Humanos , Estados Unidos/epidemiologia , Pessoa de Meia-Idade , Lipedema/diagnóstico , Edema/diagnóstico , Edema/epidemiologia , Edema/terapia , Dor/diagnóstico , Dor/epidemiologia , Fenótipo , Perna (Membro)RESUMO
BACKGROUND: The care of the vascular patient remains decentralized rather than coordinated. METHODS: We reviewed the current state of practice and published competency and care documents created by vascular professional societies. RESULTS: Vascular professional societies routinely and repeatedly endorse both a team approach and the competency of specialists from disparate training backgrounds. The care of the vascular patient does not always reflect these public endorsements. CONCLUSIONS: Centering the vascular patient as the mode of organization of care should improve care processes, expertise brought to bear, and outcomes.
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Doenças Vasculares , Humanos , Resultado do Tratamento , Atenção à SaúdeRESUMO
OBJECTIVES: The use of optimal medical therapy (OMT) in patients with chronic limb-threatening ischemia (CLTI) has not been well-studied. The Best Endovascular vs Best Surgical Therapy in Patients with CLTI study (BEST-CLI) is a multicenter, randomized, controlled trial sponsored by the National Institutes of Health comparing revascularization strategies in patients with CLTI. We evaluated the use of guideline-based OMT among patients with CLTI at the time of their enrollment into the trial. METHODS: A multidisciplinary committee defined OMT criteria related to blood pressure and diabetic management, lipid-lowering and antiplatelet medication use, and smoking status for patients enrolled in BEST-CLI. Status reports indicating adherence to OMT were provided to participating sites at regular intervals. Baseline demographic characteristics, comorbid medical conditions, and use of OMT at trial entry were evaluated for all randomized patients. A linear regression model was used to identify the relationship of predictors to the use of OMT. RESULTS: At the time of randomization (n = 1830 total enrolled), 87% of patients in BEST-CLI had hypertension, 69% had diabetes, 73% had hyperlipidemia, and 35% were currently smoking. Adherence to four OMT components (controlled blood pressure, not currently smoking, use of one lipid-lowering medication, and use of an antiplatelet agent) was modest. Only 25% of patients met all four OMT criteria; 38% met three, 24% met two, 11% met only one, and 2% met none. Age ≥80 years, coronary artery disease, diabetes, and Hispanic ethnicity were positively associated, whereas Black race was negatively associated, with the use of OMT. CONCLUSIONS: A significant proportion of patients in BEST-CLI did not meet OMT guideline-based recommendations at time of entry. These data suggest a persistent major gap in the medical management of patients with advanced peripheral atherosclerosis and CLTI. Changes in OMT adherence over the course of the trial and their impact on clinical outcomes and quality of life will be assessed in future analyses.
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Procedimentos Endovasculares , Doença Arterial Periférica , Humanos , Idoso de 80 Anos ou mais , Doença Arterial Periférica/diagnóstico , Doença Arterial Periférica/terapia , Qualidade de Vida , Resultado do Tratamento , Isquemia , Lipídeos , Fatores de Risco , Salvamento de Membro , Procedimentos Endovasculares/efeitos adversosRESUMO
BACKGROUND: Lipedema exhibits excessive lower-extremity subcutaneous adipose tissue (SAT) deposition, which is frequently misidentified as obesity until lymphedema presents. MR lymphangiography may have relevance to distinguish lipedema from obesity or lymphedema. HYPOTHESIS: Hyperintensity profiles on 3T MR lymphangiography can identify distinct features consistent with SAT edema in participants with lipedema. STUDY TYPE: Prospective cross-sectional study. SUBJECTS: Participants (48 females, matched for age [mean = 44.8 years]) with lipedema (n = 14), lipedema with lymphedema (LWL, n = 12), cancer treatment-related lymphedema (lymphedema, n = 8), and controls without these conditions (n = 14). FIELD STRENGTH/SEQUENCE: 3T MR lymphangiography (nontracer 3D turbo-spin-echo). ASSESSMENT: Review of lymphangiograms in lower extremities by three radiologists was performed independently. Spatial patterns of hyperintense signal within the SAT were scored for extravascular (focal, diffuse, or not apparent) and vascular (linear, dilated, or not apparent) image features. STATISTICAL TESTS: Interreader reliability was computed using Fleiss Kappa. Fisher's exact test was used to evaluate the proportion of image features between study groups. Multinomial logistic regression was used to assess the relationship between image features and study groups. The odds ratio (OR) and 95% confidence interval (CI) of SAT extravascular and vascular features was reported in groups compared to lipedema. The threshold of statistical significance was P < 0.05. RESULTS: Reliable agreement was demonstrated between three independent, blinded reviewers (P < 0.001). The frequency of SAT hyperintensities in participants with lipedema (36% focal, 36% diffuse), LWL (42% focal, 33% diffuse), lymphedema (62% focal, 38% diffuse), and controls (43% focal, 0% diffuse) was significantly distinct. Compared with lipedema, SAT hyperintensities were less frequent in controls (focal: OR = 0.63, CI = 0.11-3.41; diffuse: OR = 0.05, CI = 0.00-1.27), similar in LWL (focal: OR = 1.29, CI = 0.19-8.89; diffuse: OR = 1.05, CI = 0.15-7.61), and more frequent in lymphedema (focal: OR = 9.00, CI = 0.30-274.12; diffuse: OR = 5.73, CI = 0.18-186.84). DATA CONCLUSION: Noninvasive MR lymphangiography identifies distinct signal patterns indicating SAT edema and lymphatic load in participants with lipedema. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 1.
Assuntos
Lipedema , Linfedema , Feminino , Humanos , Adulto , Lipedema/diagnóstico por imagem , Linfografia/métodos , Estudos Prospectivos , Reprodutibilidade dos Testes , Estudos Transversais , Edema/diagnóstico por imagem , Linfedema/diagnóstico por imagem , Gordura Subcutânea/diagnóstico por imagem , Obesidade , Tecido Adiposo/diagnóstico por imagemRESUMO
Effective revascularization of the patient with peripheral artery disease is about more than the procedure. The approach to the patient with symptom-limiting intermittent claudication or limb-threatening ischemia begins with understanding the population at risk and variation in clinical presentation. The urgency of revascularization varies significantly by presentation; from patients with intermittent claudication who should undergo structured exercise rehabilitation before revascularization (if needed) to those with acute limb ischemia, a medical emergency, who require revascularization within hours. Recent years have seen the rapid development of new tools including wires, catheters, drug-eluting technology, specialized balloons, and biomimetic stents. Open surgical bypass remains an important option for those with advanced disease. The strategy and techniques employed vary by clinical presentation, lesion location, and lesion severity. There is limited level 1 evidence to guide practice, but factors that determine technical success and anatomic durability are largely understood and incorporated into decision-making. Following revascularization, medical therapy to reduce adverse limb outcomes and a surveillance plan should be put in place. There are many hurdles to overcome to improve the efficacy of lower extremity revascularization, such as restenosis, calcification, microvascular disease, silent embolization, and tools for perfusion assessment. This review highlights the current state of revascularization in peripheral artery disease with an eye toward technologies at the cusp, which may significantly impact current practice.
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Doença Arterial Periférica/cirurgia , Procedimentos Cirúrgicos Vasculares/tendências , Isquemia Crônica Crítica de Membro/cirurgia , Feminino , Humanos , Claudicação Intermitente/reabilitação , Claudicação Intermitente/cirurgia , Isquemia/cirurgia , Extremidade Inferior/irrigação sanguínea , Masculino , Doença Arterial Periférica/diagnóstico , Procedimentos Cirúrgicos Vasculares/métodosRESUMO
Novel targeted cancer therapies have revolutionized oncology therapies, but these treatments can have cardiovascular complications, which include heterogeneous cardiac, metabolic, and vascular sequelae. Vascular side effects have emerged as important considerations in both cancer patients undergoing active treatment and cancer survivors. Here, we provide an overview of vascular effects of cancer therapies, focusing on small-molecule kinase inhibitors and specifically inhibitors of BTK (Bruton tyrosine kinase), which have revolutionized treatment and prognosis for B-cell malignancies. Cardiovascular side effects of BTK inhibitors include atrial fibrillation, increased risk of bleeding, and hypertension, with the former 2 especially providing a treatment challenge for the clinician. Cardiovascular complications of small-molecule kinase inhibitors can occur through either on-target (targeting intended target kinase) or off-target kinase inhibition. We will review these concepts and focus on the case of BTK inhibitors, highlight the emerging data suggesting an off-target effect that may provide insights into development of arrhythmias, specifically atrial fibrillation. We believe that cardiac and vascular sequelae of novel targeted cancer therapies can provide insights into human cardiovascular biology.
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Tirosina Quinase da Agamaglobulinemia/antagonistas & inibidores , Antineoplásicos/efeitos adversos , Doenças Cardiovasculares/induzido quimicamente , Leucemia de Células B/tratamento farmacológico , Inibidores de Proteínas Quinases/efeitos adversos , Antineoplásicos/uso terapêutico , Arritmias Cardíacas/induzido quimicamente , Fibrilação Atrial/induzido quimicamente , Sobreviventes de Câncer , Hemorragia/induzido quimicamente , Humanos , Hipertensão/induzido quimicamente , Terapia de Alvo Molecular/efeitos adversos , Terapia de Alvo Molecular/métodos , Inibidores de Proteínas Quinases/uso terapêutico , Receptores de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidoresRESUMO
AIM: To test the hypothesis that glucagon-like peptide-1 receptor (GLP-1R) agonists have beneficial effects on vascular endothelial function, fibrinolysis and inflammation through weight loss-independent mechanisms. MATERIALS AND METHODS: Individuals with obesity and prediabetes were randomized to 14 weeks of the GLP-1R agonist liraglutide, hypocaloric diet or the dipeptidyl peptidase-4 inhibitor sitagliptin in a 2:1:1 ratio. Treatment with drug was double blind and placebo-controlled. Measurements were made at baseline, after 2 weeks prior to significant weight loss and after 14 weeks. The primary outcomes were measures of endothelial function: flow-mediated vasodilation (FMD), plasminogen activator inhibitor-1 (PAI-1) and urine albumin-to-creatinine ratio (UACR). RESULTS: Eighty-eight individuals were studied (liraglutide N = 44, diet N = 22, sitagliptin N = 22). Liraglutide and diet reduced weight, insulin resistance and PAI-1, while sitagliptin did not. There was no significant effect of any treatment on endothelial vasodilator function measured by FMD. Post hoc subgroup analyses in individuals with baseline FMD below the median, indicative of greater endothelial dysfunction, showed an improvement in FMD by all three treatments. GLP-1R antagonism with exendin (9-39) increased fasting blood glucose but did not change FMD or PAI-1. There was no effect of treatment on UACR. Finally, liraglutide, but not sitagliptin or diet, reduced the chemokine monocyte chemoattractant protein-1 (MCP-1). CONCLUSION: Liraglutide and diet reduce weight, insulin resistance and PAI-1. Liraglutide, sitagliptin and diet do not change FMD in obese individuals with prediabetes with normal endothelial function. Liraglutide alone lowers the pro-inflammatory and pro-atherosclerotic chemokine MCP-1, indicating that this beneficial effect is independent of weight loss.
Assuntos
Resistência à Insulina , Estado Pré-Diabético , Humanos , Incretinas/uso terapêutico , Liraglutida/uso terapêutico , Inibidor 1 de Ativador de Plasminogênio , Estado Pré-Diabético/complicações , Estado Pré-Diabético/tratamento farmacológico , Fibrinólise , Dieta Redutora , Obesidade/complicações , Obesidade/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Fosfato de Sitagliptina/uso terapêutico , Redução de Peso , Inflamação/tratamento farmacológico , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistasRESUMO
OBJECTIVE: Animal models of atherosclerosis are used extensively to interrogate molecular mechanisms in serial fashion. We tested whether a novel systems biology approach to integration of preclinical data identifies novel pathways and regulators in human disease. Approach and Results: Of 716 articles published in ATVB from 1995 to 2019 using the apolipoprotein E knockout mouse to study atherosclerosis, data were extracted from 360 unique studies in which a gene was experimentally perturbed to impact plaque size or composition and analyzed using Ingenuity Pathway Analysis software. TREM1 (triggering receptor expressed on myeloid cells) signaling and LXR/RXR (liver X receptor/retinoid X receptor) activation were identified as the top atherosclerosis-associated pathways in mice (both P<1.93×10-4, TREM1 implicated early and LXR/RXR in late atherogenesis). The top upstream regulatory network in mice (sc-58125, a COX2 inhibitor) linked 64.0% of the genes into a single network. The pathways and networks identified in mice were interrogated by testing for associations between the genetically predicted gene expression of each mouse pathway-identified human homolog with clinical atherosclerosis in a cohort of 88 660 human subjects. Homologous human pathways and networks were significantly enriched for gene-atherosclerosis associations (empirical P<0.01 for TREM1 and LXR/RXR pathways and COX2 network). This included 12(60.0%) TREM1 pathway genes, 15(53.6%) LXR/RXR pathway genes, and 67(49.3%) COX2 network genes. Mouse analyses predicted, and human study validated, the strong association of COX2 expression (PTGS2) with increased likelihood of atherosclerosis (odds ratio, 1.68 per SD of genetically predicted gene expression; P=1.07×10-6). CONCLUSIONS: PRESCIANT (Preclinical Science Integration and Translation) leverages published preclinical investigations to identify high-confidence pathways, networks, and regulators of human disease.
Assuntos
Apolipoproteínas E/genética , Aterosclerose/genética , Redes Reguladoras de Genes , Biologia de Sistemas , Adulto , Idoso , Animais , Apolipoproteínas E/deficiência , Aterosclerose/metabolismo , Aterosclerose/patologia , Modelos Animais de Doenças , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Camundongos Knockout para ApoE , Pessoa de Meia-Idade , Fenótipo , Placa Aterosclerótica , Medição de Risco , Fatores de Risco , Fatores Sexuais , Especificidade da EspécieRESUMO
Nontraumatic lower-extremity amputation is a devastating complication of peripheral artery disease (PAD) with a high mortality and medical expenditure. There are ≈150 000 nontraumatic leg amputations every year in the United States, and most cases occur in patients with diabetes. Among patients with diabetes, after an ≈40% decline between 2000 and 2009, the amputation rate increased by 50% from 2009 to 2015. A number of evidence-based diagnostic and therapeutic approaches for PAD can reduce amputation risk. However, their implementation and adherence are suboptimal. Some racial/ethnic groups have an elevated risk of PAD but less access to high-quality vascular care, leading to increased rates of amputation. To stop, and indeed reverse, the increasing trends of amputation, actionable policies that will reduce the incidence of critical limb ischemia and enhance delivery of optimal care are needed. This statement describes the impact of amputation on patients and society, summarizes medical approaches to identify PAD and prevent its progression, and proposes policy solutions to prevent limb amputation. Among the actions recommended are improving public awareness of PAD and greater use of effective PAD management strategies (eg, smoking cessation, use of statins, and foot monitoring/care in patients with diabetes). To facilitate the implementation of these recommendations, we propose several regulatory/legislative and organizational/institutional policies such as adoption of quality measures for PAD care; affordable prevention, diagnosis, and management; regulation of tobacco products; clinical decision support for PAD care; professional education; and dedicated funding opportunities to support PAD research. If these recommendations and proposed policies are implemented, we should be able to achieve the goal of reducing the rate of nontraumatic lower-extremity amputations by 20% by 2030.
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Amputação Cirúrgica/métodos , Isquemia Crônica Crítica de Membro/cirurgia , Extremidade Inferior/irrigação sanguínea , Idoso , American Heart Association , Feminino , Humanos , Masculino , Políticas , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Estados UnidosRESUMO
BACKGROUND: Patients with peripheral artery disease (PAD) are at heightened risk of acute limb ischemia (ALI), a thrombotic event associated with amputation, disability, and mortality. Previous lower extremity revascularization (LER) is associated with increased ALI risk in chronic PAD. However, the pattern of risk, clinical correlates, and outcomes after ALI early after LER are not well-studied, and effective therapies to reduce ALI post-LER are lacking. METHODS: The VOYAGER PAD trial (Vascular Outcomes Study of ASA [Acetylsalicylic Acid] Along With Rivaroxaban in Endovascular or Surgical Limb Revascularization for PAD; rNCT02504216) randomized patients with PAD undergoing LER to rivaroxaban 2.5 mg twice daily or placebo on a background of low-dose aspirin. The primary outcome was a composite of ALI, major amputation of vascular cause, myocardial infarction, ischemic stroke, or cardiovascular death. ALI was prospectively ascertained and adjudicated by a blinded committee. The cumulative incidence of ALI was calculated using Kaplan-Meier estimates, and Cox proportional hazards models were used to generate hazard ratios and associated CIs. Analyses were performed as intention-to-treat. RESULTS: Among 6564 patients followed for a median of 2.3 years, 382 (5.8%) had a total of 508 ALI events. In placebo patients, the 3-year cumulative incidence of ALI was 7.8%. After multivariable modeling, previous LER, baseline ankle-brachial index <0.50, surgical LER, and longer target lesion length were associated with increased risk of ALI. Incident ALI was associated with subsequent all-cause mortality (hazard ratio [HR], 2.59 [95% CI, 1.98-3.39]) and major amputation (HR, 24.87 [95% CI, 18.68-33.12]). Rivaroxaban reduced ALI relative to placebo by 33% (absolute risk reduction, 2.6% at 3 years; HR, 0.67 [95% CI, 0.55-0.82]; P=0.0001), with benefit starting early (HR, 0.45 [95% CI, 0.24-0.85]; P=0.0068 at 30 days). Benefit was present for severe ALI (associated with death, amputation, or prolonged hospitalization and intensive care unit stay, HR, 0.58 [95% CI, 0.40-0.83]; P=0.003) and regardless of LER type (surgical versus endovascular revascularization, P interaction=0.42) or clopidogrel use (P interaction=0.59). CONCLUSIONS: After LER for symptomatic PAD, ALI is frequent, particularly early after LER, and is associated with poor prognosis. Low-dose rivaroxaban plus aspirin reduces ALI after LER, including ALI events associated with the most severe outcomes. The benefit of rivaroxaban for ALI appears early, continues over time, and is consistent regardless of revascularization approach or clopidogrel use.
Assuntos
Isquemia/terapia , Extremidade Inferior/irrigação sanguínea , Rivaroxabana/administração & dosagem , Doença Aguda , Idoso , Aspirina/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Números Necessários para TratarRESUMO
OBJECTIVE: Amputation remains a frequent and feared outcome in patients with peripheral artery disease (PAD). Although typically characterized as major or minor on the extent of tissue loss, the etiologies and outcomes after amputation by extent are not well-understood. In addition, emerging data suggest that the drivers and outcomes of amputation in patients with PAD may differ in those with and without diabetes mellitus (DM). METHODS: The EUCLID trial randomized 13,885 patients with symptomatic PAD, including 5345 with concomitant diabetes, to ticagrelor or clopidogrel and followed them for long-term outcomes. Amputations were prospectively reported by trial investigators. Their primary and contributing drivers were adjudicated using safety data, including infection, ischemia, or multifactorial etiologies. Outcomes following major and minor amputations were analyzed, including recurrent amputation, major adverse limb events, adverse cardiovascular events, and mortality. Multivariable logistic regression models were used to identify independent predictors of minor amputations. Analyses were performed overall and stratified by the presence or absence of DM at baseline. RESULTS: Of the patients randomized, 398 (2.9%) underwent at least one lower extremity nontraumatic amputation, for a total of 511 amputations (255 major and 256 minor) over a median of 30 months. A history of minor amputation was the strongest independent predictor for a subsequent minor amputation (odds ratio, 7.29; 95% confidence interval, 5.17-10.30; P < .001) followed by comorbid DM (odds ratio, 4.60; 95% confidence interval, 3.16-6.69; P < .001). Compared with patients who had a major amputation, those with a minor amputation had similar rates of subsequent major amputation (12.2% vs 13.6%), major adverse limb events (15.1% vs 14.9%), and major adverse cardiovascular events (17.6% vs 16.3%). Ischemia alone was the primary driver of amputation (51%), followed by infection alone (27%), and multifactorial etiologies (22%); however, infection was the most frequent driver in those with DM (58%) but not in those without DM (15%). CONCLUSIONS: Outcomes after amputation remain poor regardless of whether they are categorized as major or minor. The pattern of amputation drivers in PAD differs by history of DM, with infection being the dominant etiology in those with DM and ischemia in those without DM. Greater focus is needed on the prognostic importance of minor amputation and of the multifactorial etiologies of amputation in PAD. Nomenclature with anatomical description of amputations and eliminating terms "major" or "minor" would seem appropriate.
Assuntos
Amputação Cirúrgica/efeitos adversos , Diabetes Mellitus/epidemiologia , Extremidade Inferior/irrigação sanguínea , Doença Arterial Periférica/cirurgia , Complicações Pós-Operatórias/epidemiologia , Idoso , Feminino , Seguimentos , Saúde Global , Humanos , Incidência , Masculino , Estudos Prospectivos , Taxa de Sobrevida/tendênciasRESUMO
Atherosclerosis is a chronic inflammatory vascular disease and the predominant cause of heart attack and ischemic stroke. Despite the well-known sexual dimorphism in the incidence and complications of atherosclerosis, there are relatively limited data in the clinical and preclinical literature to rigorously address mechanisms underlying sex as a biological variable in atherosclerosis. In multiple histological and imaging studies, overall plaque burden and markers of inflammation appear to be greater in men than women and are predictive of cardiovascular events. However, while younger women are relatively protected from cardiovascular disease, by the seventh decade, the incidence of myocardial infarction in women ultimately surpasses that of men, suggesting an interaction between sex and age. Most preclinical studies in animal atherosclerosis models do not examine both sexes, and even in those that do, well-powered direct statistical comparisons for sex as an independent variable remain rare. This article reviews the available data. Overall, male animals appear to have more inflamed yet smaller plaques compared to female animals. Plaque inflammation is often used as a surrogate end point for plaque vulnerability in animals. The available data support the notion that rather than plaque size, plaque inflammation may be more relevant in assessing sex-specific mechanisms since the findings correlate with the sex difference in ischemic events and mortality and thus may be more reflective of the human condition. Overall, the number of preclinical studies directly comparing plaque inflammation between the sexes is extremely limited relative to the vast literature exploring atherosclerosis mechanisms. Failure to include both sexes and to address age in mechanistic atherosclerosis studies are missed opportunities to uncover underlying sex-specific mechanisms. Understanding the mechanisms driving sex as a biological variable in atherosclerotic disease is critical to future precision medicine strategies to mitigate what is still the leading cause of death of men and women worldwide.
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Artérias , Aterosclerose , Variação Biológica da População , Disparidades nos Níveis de Saúde , Inflamação , Adulto , Fatores Etários , Idoso , Animais , Artérias/imunologia , Artérias/metabolismo , Artérias/patologia , Aterosclerose/imunologia , Aterosclerose/metabolismo , Aterosclerose/mortalidade , Aterosclerose/patologia , Modelos Animais de Doenças , Feminino , Fatores de Risco de Doenças Cardíacas , Humanos , Inflamação/imunologia , Inflamação/metabolismo , Inflamação/mortalidade , Inflamação/patologia , Masculino , Pessoa de Meia-Idade , Placa Aterosclerótica , Medição de Risco , Caracteres Sexuais , Fatores SexuaisRESUMO
[Figure: see text].
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Linfócitos T CD4-Positivos/imunologia , Doenças das Artérias Carótidas/imunologia , Coinfecção , Doença da Artéria Coronariana/imunologia , Infecções por Citomegalovirus/imunologia , Citomegalovirus/imunologia , Infecções por HIV/imunologia , Proteínas do Envelope Viral/imunologia , Adulto , Doenças Assintomáticas , Contagem de Linfócito CD4 , Linfócitos T CD4-Positivos/virologia , Doenças das Artérias Carótidas/diagnóstico por imagem , Doenças das Artérias Carótidas/virologia , Estudos de Casos e Controles , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/virologia , Estudos Transversais , Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/virologia , Epitopos , Feminino , Infecções por HIV/diagnóstico , Infecções por HIV/virologia , Fatores de Risco de Doenças Cardíacas , Humanos , Masculino , Pessoa de Meia-Idade , Placa Aterosclerótica , Medição de Risco , VasodilataçãoRESUMO
INTRODUCTION: Venous leg ulcers (VLU) embody the most severe stage of the broad spectrum of chronic venous disease. Approximately 40% of patients with VLU present with the underlying deep venous disease (DVD). Although the data are scarce, these deep venous disease-related VLU (DRV) are thought to have higher recurrence rates and a substantial economic burden. The objective of this study was to assess the economic burden of DRV across Australia, France, Germany, Italy, Spain, the UK, and the USA. METHODS: A comprehensive literature review was undertaken to identify publications documenting the incidence and prevalence of VLU and DRV, medical resource utilization, and associated costs of DRV. Findings from this literature review were used to estimate the economic burden of illness, including direct medical costs over a 12-month interval following initial presentation of a newly formed DRV. RESULTS: Total annual incidence of new or recurrent DRV in Australia, France, Germany, Italy, Spain, UK, and the US are estimated at 122,000, 263,000, 345,000, 253,000, 85,000, 230,000, and 643,000 events, respectively, in 2019. Incidence ranges from 0.73 to 3.12 per 1000 persons per year. The estimated annual direct medical costs for patients managed conservatively in these geographies total ~ $10.73 billion (USD) or $5527 per person per year. CONCLUSION: The availability of published data on the costs of VLU care varies widely across countries considered in this analysis. Although country-specific VLU practice patterns vary, there is a uniform pattern of high-cost care.
Assuntos
Estresse Financeiro , Úlcera Varicosa , França , Humanos , Incidência , Prevalência , Úlcera Varicosa/diagnóstico , Úlcera Varicosa/epidemiologia , Úlcera Varicosa/terapiaRESUMO
BACKGROUND: Paclitaxel-containing devices (PTXDs) significantly reduce reintervention in patients with symptomatic femoropopliteal peripheral artery disease. A recent aggregate-data meta-analysis reported increased late mortality in patients with peripheral artery disease treated with PTXDs. We performed an individual patient data meta-analysis to evaluate mortality. METHODS: Manufacturers of US Food and Drug Administration-approved and commercially available devices in the United States provided deidentified individual patient data for independent analysis. Cox proportional hazards 1-stage meta-analysis models using intention-to-treat methods were used for the primary analysis. A secondary analysis of recovered missing vital status data was performed. The impact of control crossover to PTXDs, cause-specific mortality, and drug dose mortality were assessed. RESULTS: A total of 2185 subjects and 386 deaths from 8 PTXD trials with 4-year median follow-up were identified. The primary analysis indicated a 38% (95% CI, 6% to 80%) increased relative mortality risk, corresponding to 4.6% absolute increase, at 5 years associated with PTXD use. Control and treatment arm loss to follow-up and withdrawal were 24% and 23%, respectively. With inclusion of recovered vital status data, the excess relative mortality risk was 27% (95% CI, 3%-58%). This observation was consistent across various scenarios, including as-treated analyses, with no evidence of increased risk over time with PTXDs. Mortality risk tended to be increased for all major causes of death. There were no subgroup differences. No drug dose-mortality association was identified. CONCLUSIONS: This individual patient data meta-analysis, based on the most complete available data set of mortality events from PTXD randomized controlled trials, identified an absolute 4.6% increased mortality risk associated with PTXD use.
Assuntos
Angioplastia com Balão/mortalidade , Análise de Dados , Stents Farmacológicos , Paclitaxel/administração & dosagem , Doença Arterial Periférica/mortalidade , Doença Arterial Periférica/terapia , Angioplastia com Balão/tendências , Stents Farmacológicos/tendências , Humanos , Mortalidade/tendências , Ensaios Clínicos Controlados Aleatórios como Assunto/métodosRESUMO
It is estimated that >2 million patients are living with an amputation in the United States. Peripheral artery disease (PAD) and diabetes mellitus account for the majority of nontraumatic amputations. The standard measurement to diagnose PAD is the ankle-brachial index, which integrates all occlusive disease in the limb to create a summary value of limb artery occlusive disease. Despite its accuracy, ankle-brachial index fails to well predict limb outcomes. There is an emerging body of literature that implicates microvascular disease (MVD; ie, retinopathy, nephropathy, neuropathy) as a systemic phenomenon where diagnosis of MVD in one capillary bed implicates microvascular dysfunction systemically. MVD independently associates with lower limb outcomes, regardless of diabetic or PAD status. The presence of PAD and concomitant MVD phenotype reveal a synergistic, rather than simply additive, effect. The higher risk of amputation in patients with MVD, PAD, and concomitant MVD and PAD should prompt aggressive foot surveillance and diagnosis of both conditions to maintain ambulation and prevent amputation in older patients.
Assuntos
Amputação Cirúrgica , Extremidade Inferior/irrigação sanguínea , Microcirculação , Doença Arterial Periférica/cirurgia , Nível de Saúde , Humanos , Doença Arterial Periférica/diagnóstico , Doença Arterial Periférica/epidemiologia , Doença Arterial Periférica/fisiopatologia , Qualidade de Vida , Fatores de Risco , Resultado do TratamentoRESUMO
Androgen deprivation therapy is a cornerstone of prostate cancer treatment. Pharmacological androgen deprivation includes gonadotropin-releasing hormone agonism and antagonism, androgen receptor inhibition, and CYP17 (cytochrome P450 17A1) inhibition. Studies in the past decade have raised concerns about the potential for androgen deprivation therapy to increase the risk of adverse cardiovascular events such as myocardial infarction, stroke, and cardiovascular mortality, possibly by exacerbating cardiovascular risk factors. In this review, we summarize existing data on the cardiovascular effects of androgen deprivation therapy. Among the therapies, abiraterone stands out for increasing risk of cardiac events in meta-analyses of both randomized controlled trials and observational studies. We find a divergence between observational studies, which show consistent positive associations between androgen deprivation therapy use and cardiovascular disease, and randomized controlled trials, which do not show these associations reproducibly.