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1.
Nutr Metab Cardiovasc Dis ; 31(5): 1533-1541, 2021 05 06.
Artigo em Inglês | MEDLINE | ID: mdl-33810961

RESUMO

BACKGROUND AND AIMS: Atherosclerotic calcification is a powerful predictor of cardiovascular disease. This study aims to determine whether circulating levels of a local/systemic calcification inhibitor or a marker of bone formation correlate with measures of coronary or extracoronary calcification. METHODS AND RESULTS: Clinical computed tomography (CT) was performed on 64 arterial disease participants undergoing carotid and lower extremity endarterectomy. Coronary artery calcium (CAC) scores and volumes were acquired from the CT scans (n = 42). CAC scores and volumes were used to derive CAC density scores. Micro-CT was performed on excised carotid (n = 36) and lower extremity (n = 31) plaques to quantify the volume and volume fraction of extracoronary calcification. Circulating levels of dephospho-uncarboxylated Matrix Gla Protein (dp-ucMGP), fetuin-A, carboxylated and uncarboxylated osteocalcin (ucOC) were quantified using commercial immunoassays. Carotid participant CAC density scores were moderately negatively correlated with plasma dp-ucMGP (rs = -0.592, P = 0.008). A weak negative association was found between CAC scores and %ucOC for all participants (rs = -0.335, P = 0.040). Another weak negative correlation was observed between fetuin-A and the volume of calcification within excised carotid specimens (rs = -0.366, P = 0.031). Despite substantial differences in coronary and extracoronary calcium measurements, the levels of circulating biomarkers did not vary significantly between carotid and lower extremity subgroups. CONCLUSION: Correlations identified between circulating biomarkers and measures of coronary and extracoronary calcium were not consistent among participant subgroups. Further research is required to determine the association between circulating biomarkers, coronary and extracoronary calcium.


Assuntos
Proteínas de Ligação ao Cálcio/sangue , Doenças das Artérias Carótidas/sangue , Doença da Artéria Coronariana/sangue , Proteínas da Matriz Extracelular/sangue , Extremidade Inferior/irrigação sanguínea , Osteocalcina/sangue , Doença Arterial Periférica/sangue , Calcificação Vascular/sangue , alfa-2-Glicoproteína-HS/análise , Idoso , Biomarcadores/sangue , Doenças das Artérias Carótidas/diagnóstico por imagem , Doenças das Artérias Carótidas/cirurgia , Angiografia por Tomografia Computadorizada , Angiografia Coronária , Doença da Artéria Coronariana/diagnóstico por imagem , Endarterectomia das Carótidas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença Arterial Periférica/diagnóstico , Doença Arterial Periférica/cirurgia , Placa Aterosclerótica , Valor Preditivo dos Testes , Calcificação Vascular/diagnóstico por imagem , Calcificação Vascular/cirurgia , Microtomografia por Raio-X
2.
Int J Mol Sci ; 22(7)2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-33808453

RESUMO

Peripheral arterial disease (PAD) of the lower extremities is a chronic illness predominantly of atherosclerotic aetiology, associated to traditional cardiovascular (CV) risk factors. It is one of the most prevalent CV conditions worldwide in subjects >65 years, estimated to increase greatly with the aging of the population, becoming a severe socioeconomic problem in the future. The narrowing and thrombotic occlusion of the lower limb arteries impairs the walking function as the disease progresses, increasing the risk of CV events (myocardial infarction and stroke), amputation and death. Despite its poor prognosis, PAD patients are scarcely identified until the disease is advanced, highlighting the need for reliable biomarkers for PAD patient stratification, that might also contribute to define more personalized medical treatments. In this review, we will discuss the usefulness of inflammatory molecules, matrix metalloproteinases (MMPs), and cardiac damage markers, as well as novel components of the liquid biopsy, extracellular vesicles (EVs), and non-coding RNAs for lower limb PAD identification, stratification, and outcome assessment. We will also explore the potential of machine learning methods to build prediction models to refine PAD assessment. In this line, the usefulness of multimarker approaches to evaluate this complex multifactorial disease will be also discussed.


Assuntos
Doença Arterial Periférica/sangue , Doença Arterial Periférica/diagnóstico , Doença Arterial Periférica/metabolismo , Biomarcadores/sangue , Humanos , Inflamação , Estimativa de Kaplan-Meier , Extremidade Inferior/irrigação sanguínea , Infarto do Miocárdio/sangue , Infarto do Miocárdio/complicações , Medição de Risco/métodos , Fatores de Risco , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/complicações
5.
Arterioscler Thromb Vasc Biol ; 41(3): 1229-1238, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33504178

RESUMO

OBJECTIVE: The aim of this study was to comprehensively assess the association of multiple lipid measures with incident peripheral artery disease (PAD). Approach and Results: We used Cox proportional hazards models to characterize the associations of each of the fasting lipid measures (total cholesterol, LDL-C [low-density lipoprotein cholesterol], HDL-C [high-density lipoprotein cholesterol], triglycerides, RLP-C [remnant lipoprotein cholesterol], LDL-TG [LDL-triglycerides], sdLDL-C [small dense LDL-C], and Apo-E-HDL [Apo-E-containing HDL-C]) with incident PAD identified by pertinent International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) hospital discharge codes (eg, 440.2) among 8330 Black and White ARIC (Atherosclerosis Risk in Communities) participants (mean age 62.8 [SD 5.6] years) free of PAD at baseline (1996-1998) through 2015. Since lipid traits are biologically correlated to each other, we also conducted principal component analysis to identify underlying components for PAD risk. There were 246 incident PAD cases with a median follow-up of 17 years. After accounting for potential confounders, the following lipid measures were significantly associated with PAD (hazard ratio per 1-SD increment [decrement for HDL-C and Apo-E-HDL]): triglycerides, 1.21 (95% CI, 1.08-1.36); RLP-C, 1.18 (1.08-1.29); LDL-TG, 1.18 (1.05-1.33); HDL-C, 1.39 (1.16-1.67); and Apo-E-HDL, 1.27 (1.07-1.51). The principal component analysis identified 3 components (1: mainly loaded by triglycerides, RLP-C, LDL-TG, and sdLDL-C; 2: by HDL-C and Apo-E-HDL; and 3: by LDL-C and RLP-C). Components 1 and 2 showed independent associations with incident PAD. CONCLUSIONS: Triglyceride-related and HDL-related lipids were independently associated with incident PAD, which has implications on preventive strategies for PAD. However, none of the novel lipid measures outperformed conventional ones. Graphic Abstract: A graphic abstract is available for this article.


Assuntos
Lipídeos/sangue , Doença Arterial Periférica/sangue , Idoso , Idoso de 80 Anos ou mais , Apolipoproteínas E/sangue , Colesterol/sangue , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Estudos de Coortes , Dislipidemias/sangue , Dislipidemias/complicações , Feminino , Humanos , Lipoproteínas/sangue , Lipoproteínas HDL/sangue , Lipoproteínas LDL/sangue , Masculino , Doença Arterial Periférica/etiologia , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Risco , Triglicerídeos/sangue
6.
Nutr Metab Cardiovasc Dis ; 31(1): 263-268, 2021 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-33500105

RESUMO

BACKGROUND AND AIM: Eicosapentaenoic acid (EPA) has been reported to improve clinical outcome of high-risk atherosclerotic patients. We investigated whether endogenous EPA values predict prognosis of peripheral artery disease (PAD) patients. METHODS AND RESULTS: This retrospective study included 166 consecutive patients who had received endovascular therapy (EVT) for PAD caused by aortoiliac artery lesions. Patients were divided into 2 groups using median preoperative EPA value (57 µg/ml): LOW EPA (n = 83) and HIGH EPA (n = 83). We compared differences between the 2 groups in prevalence of major adverse limb events (MALE) which included target lesion revascularization (TLR), non-TLR, and major amputation, and major adverse events (MAE) which included MALE and all cause death. At a median follow-up period of 20 months, MALE had occurred in 24 LOW EPA patients (28.9%) and in 12 HIGH EPA patients (14.5%) (p = 0.04), and MAE had occurred in 41 LOW EPA patients (49.4%) and in 21 HIGH EPA patients (25.3%) (p < 0.01). Kaplan-Meier analysis showed prevalence of MALE and MAE was significantly higher in LOW EPA than in HIGH EPA (long-rank test χ2 = 8.5, p < 0.01, log-rank test χ2 = 13.2, p < 0.01, respectively). Multivariate Cox regression revealed preoperative EPA value < 57 µg/ml was an independent predictor for MALE (hazard ratio [HR]: 2.70; 95% CI: 1.35 to 5.4; p < 0.01) and MAE (HR: 2.86; 95% CI: 1.67 to 4.91; p < 0.01). CONCLUSIONS: Endogenous EPA value seems to be associated with risk of MALE and MAE after EVT in patients with PAD caused by aortoiliac artery lesions.


Assuntos
Doenças da Aorta/sangue , Ácido Eicosapentaenoico/sangue , Artéria Ilíaca , Doença Arterial Periférica/sangue , Idoso , Idoso de 80 Anos ou mais , Amputação , Doenças da Aorta/diagnóstico , Doenças da Aorta/mortalidade , Doenças da Aorta/terapia , Biomarcadores/sangue , Procedimentos Endovasculares , Feminino , Humanos , Salvamento de Membro , Masculino , Pessoa de Meia-Idade , Doença Arterial Periférica/diagnóstico , Doença Arterial Periférica/mortalidade , Doença Arterial Periférica/terapia , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
7.
Angiology ; 72(5): 426-433, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33342225

RESUMO

Fabry disease is a rare X-linked lysosomal disorder. Alpha-galactosidase A deficiency caused by mutation leads to accumulation of glycosphingolipids predominantly in endothelial cells, leading to impairment of vascular wall morphology and function. We assessed vascular wall hypertrophy (carotid artery intima-media thickness, cIMT), endothelial function (brachial artery flow-mediated dilation, FMD), presence of atherosclerotic plaques in the carotid and femoral arteries, and levels of endothelial adhesion and inflammatory biomarkers in 33 Fabry patients compared with 66 healthy matched controls. Fabry patients had thicker cIMT (0.07 ± 0.02 vs 0.06 ± 0.02 cm; P = .021), as well as dilated common carotid arteries (0.80 ± 0.12 vs 0.70 ± 0.06 cm; P < .001), and aortic annulus than controls (3.07 ± 0.48 vs 2.7 ± 0.48 cm; P = .001). Flow-mediated dilation was reduced (4.48 ± 8.80 vs 10.67 ± 8.72%; P = .001) and atherosclerotic plaques were less present in Fabry patients (9.10% vs 43.94%; P < .001). Vascular cell adhesion molecule-1, interleukin-6, tumor necrosis factor α, and high-sensitivity CRP were significantly higher and E-selectin lower in Fabry patients. Our results suggest that a complex vascular phenotype is present in Fabry patients. This represents a challenge for further research that could have important clinical applications.


Assuntos
Doenças das Artérias Carótidas/etiologia , Doença de Fabry/complicações , Doença Arterial Periférica/etiologia , Adulto , Biomarcadores/sangue , Artéria Braquial/diagnóstico por imagem , Artéria Braquial/fisiopatologia , Proteína C-Reativa/análise , Doenças das Artérias Carótidas/sangue , Doenças das Artérias Carótidas/diagnóstico por imagem , Espessura Intima-Media Carotídea , Estudos de Casos e Controles , Selectina E/sangue , Doença de Fabry/diagnóstico , Feminino , Artéria Femoral/diagnóstico por imagem , Humanos , Interleucina-6/sangue , Masculino , Pessoa de Meia-Idade , Doença Arterial Periférica/sangue , Doença Arterial Periférica/diagnóstico por imagem , Doença Arterial Periférica/fisiopatologia , Placa Aterosclerótica , Eslovênia , Fator de Necrose Tumoral alfa/sangue , Molécula 1 de Adesão de Célula Vascular/sangue , Vasodilatação
8.
Int J Mol Sci ; 21(24)2020 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-33339419

RESUMO

There is an intensive effort to identify biomarkers to predict cardiovascular disease evolution. We aimed to determine the potential of microRNAs to predict the appearance of cardiovascular events (CVEs) in patients with peripheral artery disease (PAD) following femoral artery bypass surgery. Forty-seven PAD patients were enrolled and divided into two groups, without CVEs (n = 35) and with CVEs (n = 12), during 1 year follow-up. Intra-surgery atherosclerotic plaques from femoral arteries were collected and the levels of miR-142, miR-223, miR-155, and miR-92a of the primary transcripts of these microRNAs (pri-miRNAs), and gene expression of Drosha and Dicer were determined. Results showed that, in the plaques, miR-142, miR-223, and miR-155 expression levels were significantly increased in PAD patients with CVEs compared to those without CVEs. Positive correlations between these miRNAs and their pri-miRNAs levels and the Dicer/Drosha expression were observed. In the plasma of PAD patients with CVEs compared to those without CVEs, miR-223 and miR-142 were significantly increased. The multiple linear regression analyses revealed significant associations among several plasma lipids, oxidative and inflammatory parameters, and plasma miRNAs levels. Receiver operator characteristic (ROC) analysis disclosed that plasma miR-142 levels could be an independent predictor for CVEs in PAD patients. Functional bioinformatics analyses supported the role of these miRNAs in the regulation of biological processes associated with atherosclerosis. Taken together, these data suggest that plasma levels of miR-142, miR-223, miR-155, and miR-92a can significantly predict CVEs among PAD patients with good accuracy, and that plasma levels of miR-142 can be an independent biomarker to predict post-surgery CVEs development in PAD patients.


Assuntos
MicroRNAs/sangue , Doença Arterial Periférica/sangue , Placa Aterosclerótica/sangue , Complicações Pós-Operatórias/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Biomarcadores/metabolismo , Feminino , Artéria Femoral/cirurgia , Humanos , Masculino , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Doença Arterial Periférica/metabolismo , Doença Arterial Periférica/cirurgia , Placa Aterosclerótica/metabolismo , Complicações Pós-Operatórias/metabolismo , Enxerto Vascular/efeitos adversos
9.
Artigo em Inglês | MEDLINE | ID: mdl-32748882

RESUMO

Chronic cigarette smokers (CCS) are known to have elevated levels of carboxyhemoglobin (COHb). However, it is not known whether increased levels of COHb are associated with endothelial dysfunction (ED), and therefore the development of peripheral arterial disease (PAD). The aim of the study was to investigate the association of blood COHb and plasma nitric oxide (NO) levels, and whether it is an independent risk factor in the development of PAD among CCS at Dr George Mukhari Academic Hospital (DGMAH). A sample of 120 CCS with PAD and a convenience sample of 100 CCS without PAD were recruited into the study. Blood COHb levels were measured using the ABL 90 FLEX CO-oximeter automated spectroscopy. Plasma nitric oxide (NO) levels were measure using ELISA. Logistic regression analysis was used to investigate the association of blood COHb and plasma NO with PAD. Blood COHb levels of CCS with PAD were significantly higher than those of CCS without PAD, and the NO levels of CCS with PAD were significantly lower than those of CCS without PAD. Although both the blood COHb and plasma NO in CCS were significantly associated with PAD in bivariate logistic analysis, only plasma NO was independently associated with PAD in multivariate logistic analysis. This finding is consistent with the hypothesis that COHb is a cause of arterial damage in PAD, leading to reduced NO, and therefore reduced arterial dilation.


Assuntos
Carboxihemoglobina/análise , Fumar Cigarros/sangue , Óxido Nítrico/sangue , Doença Arterial Periférica/sangue , Adulto , Idoso , Artérias , Carboxihemoglobina/metabolismo , Estudos de Casos e Controles , Fumar Cigarros/efeitos adversos , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Oximetria , Doença Arterial Periférica/patologia , Fumantes
10.
PLoS One ; 15(7): e0235228, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32658909

RESUMO

PURPOSE: To assess specific risk factors and biomarkers associated with intimal arterial calcification (IAC) and medial arterial calcification (MAC). METHODS: We conducted a cross-sectional study in patients with or at risk of vascular disease from the SMART study(n = 520) and the DCS cohort(n = 198). Non-contrast computed tomography scanning of the lower extremities was performed and calcification in the femoral and crural arteries was scored as absent, predominant IAC, predominant MAC or indistinguishable. Multinomial regression models were used to assess the associations between cardiovascular risk factors and calcification patterns. Biomarkers for inflammation, calcification and vitamin K status were measured in a subset of patients with IAC(n = 151) and MAC(n = 151). RESULTS: Femoral calcification was found in 77% of the participants, of whom 38% had IAC, 28% had MAC and 11% were scored as indistinguishable. The absolute agreement between the femoral and crural arteries was high(69%). Higher age, male sex, statin use and history of coronary artery disease were associated with higher prevalences of femoral IAC and MAC compared to absence of calcification. Smoking and low ankle-brachial-index (ABI) were associated with higher prevalence of IAC and high ABI was associated with less IAC. Compared to patients with IAC, patients with MAC more often had diabetes, have a high ABI and were less often smokers. Inactive Matrix-Gla Protein was associated with increased MAC prevalence, while osteonectin was associated with decreased risk of MAC, compared to IAC. CONCLUSIONS: When femoral calcification is present, the majority of the patients have IAC or MAC throughout the lower extremity, which have different associated risk factor profiles.


Assuntos
Artéria Femoral/patologia , Doença Arterial Periférica/epidemiologia , Túnica Íntima/patologia , Túnica Média/patologia , Calcificação Vascular/epidemiologia , Idoso , Biomarcadores/sangue , Estudos Transversais , Feminino , Artéria Femoral/diagnóstico por imagem , Humanos , Extremidade Inferior/irrigação sanguínea , Masculino , Pessoa de Meia-Idade , Doença Arterial Periférica/sangue , Doença Arterial Periférica/diagnóstico , Doença Arterial Periférica/patologia , Prevalência , Medição de Risco , Fatores de Risco , Tomografia Computadorizada por Raios X , Túnica Íntima/diagnóstico por imagem , Túnica Média/diagnóstico por imagem , Calcificação Vascular/sangue , Calcificação Vascular/diagnóstico , Calcificação Vascular/patologia , Vitamina K/sangue
11.
Arterioscler Thromb Vasc Biol ; 40(9): 2018-2032, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32640905

RESUMO

OBJECTIVE: Patients with lower extremity peripheral artery disease (PAD) are at increased risk of major adverse cardiovascular events. Numerous plasma biomarkers have been investigated in lower extremity PAD, but none are used for clinical risk assessment. We aimed to provide a comprehensive overview of biomarker testing in PAD as a first step to improve risk stratification. Approach and Results: A systematic literature review in MEDLINE/PubMed, Cochrane, and Embase was performed, identifying all studies investigating plasma biomarkers in association with cardiovascular events and mortality in lower extremity PAD. Forty-seven studies comprising 21 473 PAD patients met our criteria and were included. Effect estimates were provided by the studies based on a minimum follow-up of 1 year. Meta-analyses were performed by pooling studies per biomarker for each end point. Patients with increased high-sensitivity CRP (C-reactive protein) levels had a relative risk of 1.86 (1.48-2.33) for major adverse cardiovascular events and a relative risk of 3.49 (2.35-5.19) for mortality. Increased fibrinogen and d-dimer levels were associated with an increased relative risk of mortality of 2.08 (1.46-2.97) and 2.22 (1.24-3.98), respectively. Additionally, patients with increased NT-proBNP (N-terminal pro-B-type natriuretic peptide) and high-sensitivity cTnT (cardiac troponin T) levels were at an even higher risk of mortality with relative risks of 4.50 (2.98-6.81) and 3.33 (2.70-4.10), respectively. CONCLUSIONS: This systematic review identifies promising biomarkers representing different pathophysiological processes implicated in lower extremity PAD, including high-sensitivity CRP, neutrophil-lymphocyte ratio, fibrinogen, d-dimer, NT-proBNP, and high-sensitivity cTnT. Clinical implementation should be preceded by a management study to test the utility of a combination of these markers for individual risk stratification. Ultimately, this may contribute to tailored treatment and increased effectiveness of current treatment strategies in PAD.


Assuntos
Biomarcadores/sangue , Doença Arterial Periférica/sangue , Idoso , Tomada de Decisão Clínica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença Arterial Periférica/diagnóstico , Doença Arterial Periférica/mortalidade , Doença Arterial Periférica/terapia , Valor Preditivo dos Testes , Prognóstico , Medição de Risco , Fatores de Risco
12.
Arterioscler Thromb Vasc Biol ; 40(9): 2322-2331, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32698688

RESUMO

OBJECTIVE: Inflammatory markers, such as hs-CRP (high-sensitivity C-reactive protein), have been reported to be related to peripheral artery disease (PAD). Galectin-3, a biomarker of fibrosis, has been linked to vascular remodeling and atherogenesis. However, its prospective association with incident PAD is unknown; as is the influence of inflammation on the association between galectin-3 and PAD. Approach and Results: In 9851 Atherosclerosis Risk in Communities Study participants free of PAD at baseline (1996-1998), we quantified the association of galactin-3 and hs-CRP with incident PAD (hospitalizations with PAD diagnosis [International Classification of Diseases-Ninth Revision: 440.2-440.4] or leg revascularization [eg, International Classification of Diseases-Ninth Revision: 38.18]) as well as its severe form, critical limb ischemia (PAD cases with resting pain, ulcer, gangrene, or leg amputation) using Cox models. Over a median follow-up of 17.4 years, there were 316 cases of PAD including 119 critical limb ischemia cases. Log-transformed galectin-3 was associated with incident PAD (adjusted hazard ratio, 1.17 [1.05-1.31] per 1 SD increment) and critical limb ischemia (1.25 [1.05-1.49] per 1 SD increment). The association was slightly attenuated after further adjusting for hs-CRP (1.14 [1.02-1.27] and 1.22 [1.02-1.45], respectively). Log-transformed hs-CRP demonstrated robust associations with PAD and critical limb ischemia even after adjusting for galectin-3 (adjusted hazard ratio per 1 SD increment 1.34 [1.18-1.52] and 1.34 [1.09-1.65], respectively). The addition of galectin-3 and hs-CRP to traditional atherosclerotic predictors (C statistic of the base model 0.843 [0.815-0.871]) improved the risk prediction of PAD (ΔC statistics, 0.011 [0.002-0.020]). CONCLUSIONS: Galectin-3 and hs-CRP were independently associated with incident PAD in the general population, supporting the involvement of fibrosis and inflammation in the pathophysiology of PAD.


Assuntos
Proteína C-Reativa/análise , Galectina 3/sangue , Mediadores da Inflamação/sangue , Claudicação Intermitente/sangue , Isquemia/sangue , Doença Arterial Periférica/sangue , Idoso , Biomarcadores/sangue , Estado Terminal , Feminino , Fibrose , Humanos , Incidência , Claudicação Intermitente/diagnóstico , Claudicação Intermitente/epidemiologia , Claudicação Intermitente/terapia , Isquemia/diagnóstico , Isquemia/epidemiologia , Isquemia/terapia , Masculino , Pessoa de Meia-Idade , Doença Arterial Periférica/diagnóstico , Doença Arterial Periférica/epidemiologia , Doença Arterial Periférica/terapia , Prognóstico , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Estados Unidos
13.
Expert Opin Pharmacother ; 21(13): 1603-1616, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32558590

RESUMO

INTRODUCTION: Peripheral artery disease (PAD) is a prevalent but underdiagnosed manifestation of atherosclerosis that has a worse prognosis than coronary artery disease. Patients with PAD are at heightened risk of both systemic cardiovascular adverse events and limb-related morbidity. There is insufficient awareness of its clinical manifestations, including intermittent claudication and critical limb ischemia and of its risk of adverse cardiovascular and limb outcomes. AREAS COVERED: The authors present the current knowledge concerning medications and their mechanism of action, landmark trials, and the evidence base behind the most commonly utilized pharmacological therapy including but not limited aspirin, clopidogrel, ticagrelor, warfarin, rivaroxaban, statins, angiotensin-converting enzyme inhibitors, Evolocumab and Ezetimibe. EXPERT OPINION: Relative to coronary artery disease, peripheral artery disease is an undertreated and under-investigated condition. The majority of the evidence base in the management of PAD is extrapolated from data subsets of large trials examining different conditions. This creates a paucity of management decisions based on trials powered for outcomes in PAD.


Assuntos
Anticoagulantes/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Doença Arterial Periférica/tratamento farmacológico , Inibidores da Agregação Plaquetária/uso terapêutico , Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Claudicação Intermitente/tratamento farmacológico , Doença Arterial Periférica/sangue , Doença Arterial Periférica/etiologia , Fatores de Risco
14.
Rev Assoc Med Bras (1992) ; 66(3): 268-274, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32520144

RESUMO

OBJECTIVE: To investigate the association between low serum vitamin D levels and peripheral arterial disease (PAD). METHODS: A cross-sectional study with a consecutive sample of 133 individuals from Caxias do Sul, Brasil. We considered PAD patients those with an ankle-brachial index (ABI) ≤ 0.90 or with arterial revascularization. Vitamin D serum level was categorized as sufficient (≥30 ng/mL), insufficient (>20 to 29 ng/mL), and deficient (<20 ng/mL). Prevalence ratios (RP) were calculated through Poisson regression. RESULTS: The prevalence of PAD was 50.7% (95% CI 42-59). After adjustment for potential PAD risk factors, RP were 1.08 (95% CI 0.66-1.76) for insufficient serum level and 1.57 (95% CI 0.96-2.57) for deficient vitamin D serum level; (p for trend = 0.020). CONCLUSION: Vitamin D serum levels showed an inverse and significant dose-response relationship with PAD.


Assuntos
Doença Arterial Periférica/sangue , Doença Arterial Periférica/etiologia , Deficiência de Vitamina D/complicações , Vitamina D/sangue , Adulto , Índice Tornozelo-Braço , Brasil/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença Arterial Periférica/epidemiologia , Prevalência , Fatores de Risco , Vitamina D/uso terapêutico , Deficiência de Vitamina D/sangue
15.
Cardiovasc Diabetol ; 19(1): 75, 2020 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-32527273

RESUMO

BACKGROUND: Although an increased arterial stiffness has been associated with traditional coronary risk factors, the risk factors and pathology of arterial stiffness remain unclear. In this study, we aimed to identify the plasma metabolites associated with arterial stiffness in patients with type 2 diabetes mellitus. METHODS: We used the metabolomic data of 209 patients with type 2 diabetes as the first dataset for screening. To form the second dataset for validation, we enlisted an additional 31 individuals with type 2 diabetes. The non-targeted metabolome analysis of fasting plasma samples using gas chromatography coupled with mass spectrometry and the measurement of brachial-ankle pulse wave velocity (baPWV) were performed. RESULTS: A total of 65 annotated metabolites were detected. In the screening dataset, there were statistically significant associations between the baPWV and plasma levels of indoxyl sulfate (r = 0.226, p = 0.001), mannitol (r = 0.178, p = 0.010), mesoerythritol (r = 0.234, p = 0.001), and pyroglutamic acid (r = 0.182, p = 0.008). Multivariate regression analyses revealed that the plasma levels of mesoerythritol were significantly (ß = 0.163, p = 0.025) and that of indoxyl sulfate were marginally (ß = 0.124, p = 0.076) associated with baPWV, even after adjusting for traditional coronary risk factors. In the independent validation dataset, there was a statistically significant association between the baPWV and plasma levels of indoxyl sulfate (r = 0.430, p = 0.016). However, significant associations between the baPWV and plasma levels of the other three metabolites were not confirmed. CONCLUSIONS/INTERPRETATION: The plasma levels of indoxyl sulfate were associated with arterial stiffness in Japanese patients with type 2 diabetes. Although the plasma levels of mannitol, mesoerythritol, and pyroglutamic acid were also associated with arterial stiffness, further investigation is needed to verify the results.


Assuntos
Diabetes Mellitus Tipo 2/sangue , Indicã/sangue , Doença Arterial Periférica/sangue , Rigidez Vascular , Idoso , Índice Tornozelo-Braço , Biomarcadores/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/fisiopatologia , Eritritol/análogos & derivados , Eritritol/sangue , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Masculino , Manitol/sangue , Metabolômica , Pessoa de Meia-Idade , Doença Arterial Periférica/diagnóstico , Doença Arterial Periférica/fisiopatologia , Ácido Pirrolidonocarboxílico/sangue
16.
Vascular ; 28(5): 629-642, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32366176

RESUMO

OBJECTIVES: Regulatory T cells (Tregs) mediate immunomodulation and protect against atherosclerosis. It is considered that reducing the amount of pro-inflammatory mediators could be achieved by enhancing the anti-inflammatory response, and this may be considered one of the main targets for therapy development. The inhibitory cytokines secreted by Tregs mainly include interleukin-10 (IL-10) and transforming growth factor-beta (TGF-ß). Based on its known immunosuppressive involvement with other inflammatory disorders, we hypothesized that the newly characterized cytokine interleukin-37 (IL-37) might be associated with the inhibitory functions of Treg in atherosclerosis. Immune regulatory functions of IL-37 have not been completely clarified. Accordingly, we speculated that IL-37 might play a regulatory role in the immunosuppression of Tregs in atherosclerotic disease. METHODS: Real-time polymerase chain reaction and enzyme linked immunosorbent assay were used to test gene expression and protein levels of IL-37 in peripheral blood and localized freshly resected arterial tissues from 84 patients with peripheral arterial occlusive disease and 50 non-atherosclerotic subjects. Results were correlated to disease hallmarks. We also evaluated the ability of recombinant IL-37 to modulate Treg cytokine secretion and T cell inhibition in relation to atherosclerotic disorder in vitro.Results: Our results revealed that IL-37 was increased in patients with chronic lower limb atherosclerotic ischemia, compared to non-atherosclerotic controls. In addition, the expression levels of circulating IL-37 correlated with disease severity of chronic lower limb ischemia. Supplementation with rIL-37 augmented levels of released IL-10 and TGF-ß in supernatants of T cells co-cultured with Tregs in the enrolled patients.Conclusions: Results suggest a role for IL-37 in mediating anti-inflammatory functions in the atherosclerotic process, potentially involving enhancement of Treg inhibitory function and anti-inflammatory cytokine secretion with a particularly marked direct response in severe disease.


Assuntos
Interleucina-1/sangue , Isquemia/sangue , Doença Arterial Periférica/sangue , Linfócitos T Reguladores/metabolismo , Adulto , Idoso , Estudos de Casos e Controles , Células Cultivadas , Técnicas de Cocultura , Feminino , Humanos , Interleucina-1/genética , Interleucina-1/farmacologia , Interleucina-10/metabolismo , Isquemia/diagnóstico , Isquemia/imunologia , Masculino , Pessoa de Meia-Idade , Doença Arterial Periférica/diagnóstico , Doença Arterial Periférica/imunologia , Fenótipo , Linfócitos T Reguladores/efeitos dos fármacos , Linfócitos T Reguladores/imunologia , Fator de Crescimento Transformador beta/metabolismo
17.
Vascular ; 28(6): 731-738, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32437240

RESUMO

BACKGROUND: Peripheral arterial disease is associated with increased cardiovascular mortality and morbidity. C-reactive protein and albumin are biomarkers of inflammation and malnutrition that play key roles in the pathophysiological pathways involved in the progression of atherosclerosis and peripheral arterial disease. In this study, we aimed to assess the relationship between C-reactive protein to albumin ratio and the suprapopliteal peripheral arterial disease severity and complexity as assessed by TransAtlantic Inter-Society Consensus-II (TASC-II) classification. METHOD: Our study enrolled 224 consecutive patients referred for peripheral angiography with the clinical features of possible peripheral arterial disease at a tertiary care center between January 2016 and September 2019. Level of disease and lesion characteristics were defined with reference to angiographic findings according to the TASC-II classification. RESULTS: C-reactive protein/albumin ratio levels were significantly higher in TASC-II class C and D than in TASC-II class B patients with a median level of 1.8 to 2.1 vs 1.4, respectively (p = 0.018). In multivariate regression analysis, C-reactive protein to albumin ratio remained an independent predictor of severe peripheral arterial disease. The predictive performance of C-reactive protein to albumin ratio, C-reactive protein, and albumin were compared by Receiver Operating Characteristic curve analysis. C-reactive protein to albumin ratio surpassed C-reactive protein and albumin in predicting peripheral arterial disease severity and complexity. A level of C-reactive protein to albumin ratio > 0.14 predicted a higher grade of suprapopliteal TASC-II class with sensitivity and specificity of 68.2% and 56.0%, respectively. CONCLUSION: C-reactive protein to albumin ratio was strongly associated with peripheral arterial disease severity and complexity, as assessed by TASC-II classification. Also, C-reactive protein to albumin ratio was found to be a more accurate marker than C-reactive protein and albumin alone in predicting more severe and complex lesions in patients with peripheral arterial disease.


Assuntos
Angiografia , Proteína C-Reativa/análise , Doença Arterial Periférica/sangue , Doença Arterial Periférica/diagnóstico por imagem , Albumina Sérica Humana/análise , Biomarcadores/sangue , Estudos Transversais , Humanos , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Estudos Retrospectivos , Índice de Gravidade de Doença
18.
Vascular ; 28(6): 715-721, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32408853

RESUMO

OBJECTIVES: To determine the association of pre- and postinterventional serum levels of interleukin-6 and high-sensitivity C-reactive protein at the six-month evaluation of restenosis after stenting of the femoropopliteal artery. METHODS: Sixty-eight consecutive patients with steno-occlusive femoropopliteal artery disease of Rutherford category III or IV who underwent stent implantation were included. Six-month patency was evaluated with color-coded duplex ultrasound. The association of in-stent restenosis with interleukin-6 and high-sensitivity C-reactive protein levels at baseline, and 24-h postintervention was assessed with a multivariate logistic regression analysis. RESULTS: In-stent restenosis was found in 15 patients (22.1%) within six months. Interleukin-6 and high-sensitivity C-reactive protein levels were significantly increased at 24-h postintervention compared to their preintervention values (p < 0.001 and p = 0.002, respectively). Interleukin-6 values at baseline (odds ratio, 1.11; 95% confidence interval: 1.00, 1.23; p = 0.044) and 24-h postintervention (odds ratio, 1.04; 95% confidence interval: 1.02, 1.06; p < 0.001) were independently associated with six-month in-stent restenosis. Twenty-four-hour postinterventional high-sensitivity C-reactive protein levels were also found to be related to restenosis (odds ratio, 1.15; 95% confidence interval: 1.04, 1.26; p = 0.006), but high-sensitivity C-reactive protein levels at baseline did not show an independent association with in-stent restenosis (odds ratio, 0.57; 95% confidence interval: 0.35, 1.80; p = 0.667). Smoking, diabetes mellitus, and cumulative stent length were other parameters associated with an increased risk for in-stent restenosis. CONCLUSIONS: Femoropopliteal artery angioplasty with stent placement induces an inflammatory response. Interleukin-6 is a powerful independent predictor of intermediate-term outcomes for stenting of the femoropopliteal artery, suggesting that its predictive value may be superior to that of high-sensitivity C-reactive protein.


Assuntos
Angioplastia/instrumentação , Proteína C-Reativa/metabolismo , Artéria Femoral , Interleucina-6/sangue , Doença Arterial Periférica/terapia , Artéria Poplítea , Stents , Idoso , Idoso de 80 Anos ou mais , Angioplastia/efeitos adversos , Biomarcadores/sangue , Feminino , Artéria Femoral/diagnóstico por imagem , Artéria Femoral/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Doença Arterial Periférica/sangue , Doença Arterial Periférica/diagnóstico por imagem , Doença Arterial Periférica/fisiopatologia , Artéria Poplítea/diagnóstico por imagem , Artéria Poplítea/fisiopatologia , Valor Preditivo dos Testes , Estudos Prospectivos , Recidiva , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Grau de Desobstrução Vascular
19.
Vascular ; 28(5): 513-519, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32390562

RESUMO

OBJECTIVES: Lower extremity peripheral artery disease develops mainly due to atherosclerosis and occurs as a result of the systemic atherosclerotic process. Increased triglyceride (TG) and decreased high density lipoprotein cholesterol (HDL-C) values increase atherosclerosis risk. With regard to this information, TG/HDL-C ratio is used as the atherogenic index. The aim of the present study was to evaluate the role of TG/HDL-C ratio to predict the complexity of disease in patients with peripheral artery disease. METHODS: Patients who were diagnosed with peripheral artery disease and admitted to our clinic between August 2013 and August 2019 were included in this study retrospectively. Patients were divided into two groups based on angiographic evaluations with TransAtlantic Inter-Society Consensus-II classification. Those with TASC A-B lesions were included in Group 1 and those with TASC C-D lesions constituted Group 2. RESULTS: The mean ages of Group 1 (n = 314) and Group 2 (n = 98) patients were 56.1 ± 9.3 and 58.4.1 ± 8.1 years, respectively. The frequency of male gender and coronary artery disease was significantly higher in Group 2 (p = 0.043, p = 0.001, respectively). In Group 2, triglyceride and TG/HDL-C ratios were significantly high, while HDL-C was significantly low (p = 0.022, p < 0.001, p = 0.010, respectively). The multivariate logistic regression analysis performed to evaluate the parameters in predicting the angiographic complexity of peripheral artery disease showed that coronary artery disease (OR: 1.009 CI 95%: 1.003-1.021 p = 0.016) and TG/HDL-C ratio (OR: 5.385 CI 95%: 2.553-9.357 p = 0.001) were independent predictors for complexity. ROC analysis revealed that the cut-off value of TG/HDL-C was 2.9 (AUC = 0.670, p < 0.001) with 75.5% sensitivity and 56.7% specificity. CONCLUSIONS: It is possible to predict the angiographic complexity of peripheral artery disease with TG/HDL-C ratio, also known as atherogenic index, which is easily obtained by routine biochemical parameters.


Assuntos
Análise Química do Sangue , HDL-Colesterol/sangue , Doença Arterial Periférica/diagnóstico , Placa Aterosclerótica , Triglicerídeos/sangue , Idoso , Angiografia , Biomarcadores/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença Arterial Periférica/sangue , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Índice de Gravidade de Doença
20.
Vascular ; 28(6): 708-714, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32393108

RESUMO

OBJECTIVES: While the use of protamine sulfate as a heparin reversal agent has been extensively reviewed in patients undergoing carotid endarterectomy and coronary artery bypass grafting, there is a lack of literature on protamine's effects on lower extremity bypasses. The purpose of this study was to determine the risk of protamine sulfate dosing after tibial bypass on thrombotic or bleeding events, including early bypass failure. METHODS: We performed a retrospective review of our institutional database for patients undergoing primary distal peripheral bypass from January 2009 through December 2015 (contralateral bypass was considered to be a new primary bypass). Primary endpoints include composite thrombotic events (myocardial infarction, stroke, amputation at 30 days and patency less than 30 days) and composite bleeding events (bleeding or transfusion). RESULTS: A total of 152 tibial or peroneal bypasses in 136 patients with critical limb ischemia were identified. Of these, 78 (57.4%) patients received protamine sulfate intraoperatively and 58 (42.6%) did not. There were no differences in composite thrombotic or hemorrhagic outcomes. Protamine use had no effect on the rates of perioperative MI (9.0% versus 3.5%, p = 0.20), stroke (1.3% versus 1.7%, p = 0.83), or perioperative mortality (5.1% versus 3.5%, p = 0.64). There was no significant difference in composite post-operative bleeding events (20.7% versus 14.1%, p = 0.31) or composite thrombotic events (17.2% versus 18.0%, p = 0.91). Patients who received protamine undergoing bypass with non-autogenous conduit had significantly higher-recorded median operative blood loss (250 mL versus 150 mL, p = 0.0097) and median procedure lengths (265 min versus 201 min, p = 0.0229). No difference in 30-day amputation-free survival was noted (91.0% versus 91.4%, p = 0.94). Follow-up Kaplan-Meier estimation did not demonstrate a difference in 30-day patency (91.7% versus 88.5%, p = 0.52). CONCLUSIONS: Heparin reversal with protamine sulfate after tibial or peroneal bypass grafting is not associated with higher cardiovascular morbidity, bypass thrombosis, amputation, or mortality. Additionally, there was no statistically significant difference in post-operative bleeding or thrombosis complications for patients who did not receive protamine, although the findings are suggestive of a potential difference in a more adequately powered study. Our results suggest that protamine sulfate is safe for intraoperative use without increased risk of thrombotic complications or early tibial bypass graft failure.


Assuntos
Antagonistas de Heparina/administração & dosagem , Doença Arterial Periférica/cirurgia , Protaminas/administração & dosagem , Artérias da Tíbia/cirurgia , Enxerto Vascular , Grau de Desobstrução Vascular , Bases de Dados Factuais , Feminino , Oclusão de Enxerto Vascular/diagnóstico por imagem , Oclusão de Enxerto Vascular/etiologia , Oclusão de Enxerto Vascular/fisiopatologia , Antagonistas de Heparina/efeitos adversos , Humanos , Masculino , Doença Arterial Periférica/sangue , Doença Arterial Periférica/diagnóstico , Doença Arterial Periférica/fisiopatologia , Hemorragia Pós-Operatória/etiologia , Protaminas/efeitos adversos , Estudos Retrospectivos , Fatores de Risco , Trombose/diagnóstico por imagem , Trombose/etiologia , Trombose/fisiopatologia , Artérias da Tíbia/diagnóstico por imagem , Artérias da Tíbia/fisiopatologia , Fatores de Tempo , Resultado do Tratamento , Enxerto Vascular/efeitos adversos
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