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1.
Angiology ; 71(4): 340-348, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32013527

RESUMO

We evaluated the relationship between serum bilirubin levels and ankle-brachial index (ABI) to determine whether gender affected the relationship between bilirubin levels and peripheral arterial disease (PAD) in patients with hypertension. A total of 543 patients were included in our studies (78 patients with PAD and 465 without PAD). Peripheral arterial disease was defined as ABI <0.90 for either and/or both sides. Serum bilirubin levels were measured with a vanadate oxidation method by using fasting venous blood samples. Serum total bilirubin (TBiL) and direct bilirubin (DBiL) levels were higher in males compared with females (both P < .05). Total bilirubin and DBiL were significantly lower in the PAD group. After adjustment for cardiovascular risk factors, PAD was independently negatively related to TBiL and DBiL, with odds ratios (OR) 0.914 (95% confidence interval [CI]: 0.845-0.990) and 0.748 (95% CI: 0.572-0.977). In addition, there was a relationship between PAD and bilirubin levels (TBiL-OR = 0.884, 95% CI: 0.792-0.985; DBiL-OR = 0.621; 95% CI: 0.424-0.909) only in males but not in females. Future studies should further evaluate whether interventions that increase serum bilirubin levels will have a particular role in PAD prevention in males.


Assuntos
Bilirrubina/sangue , Hipertensão/sangue , Hipertensão/fisiopatologia , Doença Arterial Periférica/sangue , Doença Arterial Periférica/fisiopatologia , Índice Tornozelo-Braço , Biomarcadores/sangue , China , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores Sexuais
2.
Curr Cardiol Rep ; 22(3): 13, 2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-31997026

RESUMO

The PAD population is at increased risk of major adverse cardiovascular events (MACE) and major adverse limb events (MALE). Risk factor modification, symptom control, antithrombotic, and lipid therapies are the mainstays of PAD medical therapy. Recent data has challenged prior recommendations regarding the optimal secondary prevention strategies in PAD. PURPOSE OF REVIEW: To review clinical evidence from large randomized controlled trials showing the benefit of antithrombotic and lipid therapy in the PAD population. RECENT FINDINGS: The COMPASS trial challenged prior recommendations regarding anticoagulation in PAD. Among the PAD subgroup, rivaroxaban 2.5 mg plus aspirin reduced MACE (HR 0.72, 95% CI 0.57-0.90, p = 0.0047), MALE (HR 0.54, 95% CI 0.35-0.82, p = 0.0037), and major amputation (HR 0.30, 95% CI 0.11-0.80, p = 0.011) compared with aspirin monotherapy. The THEMIS trial showed a 55% risk reduction for MALE with ticagrelor DAPT compared with aspirin monotherapy (HR 0.45, 95% CI 0.23-0.86). The FOURIER trial revealed that lowering LDL cholesterol below current targets with a PCSK9 inhibitor reduced MACE (HR 0.73, 95% CI 0.59-0.91, p = 0.0040) and MALE (HR 0.43, 95% CI 0.19-0.99, p = 0.042) in subjects with symptomatic PAD. Recent high-quality evidence shows the benefit of antiplatelet therapy, anticoagulation therapy, and lipid therapy in reducing MACE and MALE in PAD. Despite these findings, implementation remains a challenge and focus should now shift towards adopting evidence-based recommendations in clinical practice.


Assuntos
Fibrinolíticos/uso terapêutico , Doença Arterial Periférica/tratamento farmacológico , Inibidores da Agregação de Plaquetas/uso terapêutico , Humanos , Doença Arterial Periférica/sangue , Doença Arterial Periférica/diagnóstico , Pró-Proteína Convertase 9 , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco , Resultado do Tratamento
3.
Ann Vasc Surg ; 62: 356-364, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30802587

RESUMO

BACKGROUND: The aim of this study was to evaluate the long-term outcomes of spinal cord stimulation in patients with critical limb ischemia and to test the hypothesis that the dynamics of clinical changes one year after therapy depend both on the clinical determinants associated with the underlying disease and on factors related to systemic atherosclerosis. METHODS: This prospective cohort study included 56 patients with critical limb ischemia. All patients before and after spinal cord stimulation were examined in terms of the dynamics of their clinical changes using the Rutherford scale and transcutaneous oxygen tension (TcPO2, mm Hg) in the affected foot. The active orthostatic test was used to assess the functional state of peripheral perfusion. RESULTS: One year after spinal cord stimulation, 74% of patients showed positive clinical outcomes. No changes were observed in 9.3% of patients, whereas adverse clinical outcomes were revealed in 16.7% of cases. The TcPO2 values were significantly reduced before spinal cord stimulation: 10.5 (6.4-16.0) mm Hg. The functional status of the peripheral microvasculature was also disturbed. One year after therapy, TcPO2 significantly increased and the adaptive mechanisms of the microvasculature were improved in more than 70% of patients. Logistic regression analysis showed that the initially low TcPO2 values (<10 mm Hg) with a lack of gain in TcPO2 during the orthostatic test are associated with the negative clinical outcomes after spinal cord stimulation. The gain in TcPO2 during the orthostatic test to >10 mm Hg is associated with the positive clinical outcomes after spinal cord stimulation. The age-adjusted Charlson Comorbidity Index >5 and duration of critical ischemic symptoms also had a negative effect on the clinical outcomes after spinal cord stimulation. CONCLUSIONS: The positive clinical outcomes were revealed in most patients with critical limb ischemia one year after spinal cord stimulation. The low values of peripheral tissue metabolism with the disturbed functional status of the microvasculature are associated with the negative clinical outcome. The patients with baseline TcPO2 <10 mm Hg can recover if they still have a sufficient microcirculatory reserve capacity. Duration of critical ischemic symptoms and high comorbidity burden with allowance for age are negative factors affecting the clinical outcome.


Assuntos
Isquemia/terapia , Doença Arterial Periférica/terapia , Estimulação da Medula Espinal , Idoso , Biomarcadores/sangue , Monitorização Transcutânea dos Gases Sanguíneos , Estado Terminal , Feminino , Humanos , Isquemia/sangue , Isquemia/diagnóstico , Isquemia/fisiopatologia , Masculino , Microcirculação , Pessoa de Meia-Idade , Oxigênio/sangue , Doença Arterial Periférica/sangue , Doença Arterial Periférica/diagnóstico , Doença Arterial Periférica/fisiopatologia , Estudos Prospectivos , Recuperação de Função Fisiológica , Fluxo Sanguíneo Regional , Fatores de Tempo , Resultado do Tratamento
4.
Clin Cardiol ; 42(10): 908-913, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31368589

RESUMO

BACKGROUND: Peripheral artery disease (PAD) is common, and although it is associated with cardiovascular (CV) morbidity, mortality, reduced quality of life, and increased health care burden, PAD data are relatively scarce. Elevated triglycerides (TG) are associated with and are a risk factor for PAD. HYPOTHESIS: Large administrative retrospective data may provide further insight into the relationship between hypertriglyceridemia and peripheral arterial revascularization in high-risk statin-treated patients. METHODS: This retrospective administrative claims analysis of the Optum Research Database included statin-treated patients aged ≥45 years with diabetes and/or atherosclerotic CV disease enrolled in 2010 and followed for ≥6 months. Patients with TG ≥150 mg/dL were propensity score-matched to a comparator cohort with TG <150 mg/dL and high-density lipoprotein cholesterol >40 mg/dL (n = 23 181 in each cohort). A sub-analysis was conducted in patients with TG 200-499 mg/dL and a matched comparator cohort (n = 10 990). Clustered P-values were calculated using a Cox proportional hazard model with cohort as the independent variable (α, 0.05). RESULTS: Multivariate analysis showed a 37% higher rate of peripheral arterial revascularization in the elevated-TG cohort vs the comparator cohort (hazard ratio [HR] 1.370, 95% confidence interval [CI] 1.263-1.486; P < .001). Results in the high-TG sub-cohort were similar, with a 49% higher rate of revascularization vs the comparator cohort (HR 1.489; 95% CI, 1.348-1.644; P < .001). CONCLUSIONS: This large administrative retrospective analysis of high-risk statin-treated patients showed that elevated TG (≥150 mg/dL) and high TG (200-499 mg/dL) were significant predictors of peripheral arterial revascularization; this warrants further study.


Assuntos
Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Hipertrigliceridemia/complicações , Doença Arterial Periférica/etiologia , Medição de Risco/métodos , Triglicerídeos/sangue , Biomarcadores/sangue , Causas de Morte/tendências , Feminino , Humanos , Hipertrigliceridemia/sangue , Masculino , Pessoa de Meia-Idade , Morbidade/tendências , Doença Arterial Periférica/sangue , Doença Arterial Periférica/epidemiologia , Pontuação de Propensão , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida/tendências , Estados Unidos/epidemiologia
5.
Nutrients ; 11(9)2019 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-31450550

RESUMO

l-carnitine is an important co-factor in fatty-acid metabolism, and its deficiency is associated with insulin resistance, which is independently associated with arterial stiffness. This study evaluated the relationship between serum l-carnitine level and peripheral arterial stiffness (PAS) in kidney transplantation (KT). Fasting blood samples were collected from 65 patients who underwent KT. We measured the brachial-ankle pulse wave velocity, and 36 patients (55.4%) had PAS. Patients with PAS had a significantly higher percentage of diabetes (p = 0.001), hypertension (p = 0.033), and metabolic syndrome (p = 0.044); higher waist circumference (p = 0.010), systolic blood pressure (p = 0.002), serum triglyceride level (p = 0.040), insulin level (p = 0.002), and homeostasis model assessment of insulin resistance (p = 0.002); lower high-density lipoprotein cholesterol (p = 0.036) and serum l-carnitine levels (p < 0.001); older age (p = 0.041); and a longer KT duration (p = 0.025) than those without PAS. Statistical analysis revealed an independent association between PAS in KT and KT duration (95% confidence interval (CI): 1.003-1.054, p = 0.029) and serum l-carnitine levels (95% CI: 0.842-0.998, p = 0.044). The area under the receiver operating characteristic curve indicated that the diagnostic power of l-carnitine to predict PAS was 0.789 (95% CI: 0.670-0.881, p < 0.001). Serum-free l-carnitine level is negatively associated with PAS in patients who undergo KT.


Assuntos
Nefropatias/cirurgia , Transplante de Rim , Doença Arterial Periférica/diagnóstico , Rigidez Vascular , Adulto , Índice Tornozelo-Braço , Biomarcadores/sangue , Carnitina/sangue , Estudos Transversais , Regulação para Baixo , Feminino , Humanos , Nefropatias/sangue , Nefropatias/diagnóstico , Nefropatias/fisiopatologia , Masculino , Pessoa de Meia-Idade , Doença Arterial Periférica/sangue , Doença Arterial Periférica/fisiopatologia , Valor Preditivo dos Testes , Reprodutibilidade dos Testes
6.
Nutr Metab Cardiovasc Dis ; 29(10): 1068-1076, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31378630

RESUMO

BACKGROUND AND AIM: Heterozygous familial hypercholesterolemia (HeFH) is a genetic disease characterized by a heterogeneous phenotype. The assessment of cardiovascular (CV) risk is challenging for HeFH. Cholesterol burden (CB) allows to estimate the lifelong exposure to high levels of cholesterol. The aim of this study was to analyze the distribution of subclinical atherosclerosis and the relationship between atherosclerosis and the CB in a sample of HeFH patients, focusing on sex-related differences. METHODS AND RESULTS: 154 asymptomatic HeFH subjects underwent coronary-artery-calcium score (CACs) and Doppler ultrasound of carotid and femoral arteries. Yearly lipid profiles and HeHF history were obtained from patients' files in order to calculate total CB. Atherosclerotic burden was defined by the presence of CACs > 0 or by the presence of carotid or femoral plaque. Study population was stratified according to gender. The prevalence of CAC, carotid and femoral atherosclerosis was of 62%, 55% and 56%, respectively. Coronary district was the least involved in women, who had a higher prevalence in carotid atherosclerosis. When two vascular districts were affected, women had an increased prevalence of femoral and carotid atherosclerosis whereas men had a higher prevalence of coronary and femoral atherosclerosis. CB correlated to the presence of atherosclerosis in any of the three vascular districts with a significant increasing trend depending on the number of affected areas. CONCLUSIONS: A polyvascular atherosclerotic burden is found in asymptomatic HeFH patients. Gender differences in the territory distribution were observed. The early and lasting exposure to high cholesterol, as expressed by CB, is a major determinant of atherosclerotic burden.


Assuntos
Doenças das Artérias Carótidas/epidemiologia , Colesterol/sangue , Doença da Artéria Coronariana/epidemiologia , Hiperlipoproteinemia Tipo II/epidemiologia , Doença Arterial Periférica/epidemiologia , Adulto , Idoso , Doenças Assintomáticas , Biomarcadores/sangue , Doenças das Artérias Carótidas/sangue , Doenças das Artérias Carótidas/diagnóstico por imagem , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/diagnóstico , Estudos Transversais , Feminino , Artéria Femoral/diagnóstico por imagem , Predisposição Genética para Doença , Humanos , Hiperlipoproteinemia Tipo II/sangue , Hiperlipoproteinemia Tipo II/diagnóstico , Hiperlipoproteinemia Tipo II/genética , Masculino , Pessoa de Meia-Idade , Paris/epidemiologia , Doença Arterial Periférica/sangue , Doença Arterial Periférica/diagnóstico por imagem , Fenótipo , Prevalência , Prognóstico , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença , Fatores Sexuais , Fatores de Tempo , Adulto Jovem
7.
Vasc Med ; 24(5): 414-421, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31277561

RESUMO

Extensive atherosclerotic plaque burden in the lower extremities often leads to symptomatic peripheral artery disease (PAD) including impaired walking performance and claudication. Interleukin-1ß (IL-1ß) may play an important pro-inflammatory role in the pathogenesis of this disease. Interruption of IL-1ß signaling was hypothesized to decrease plaque progression in the leg macrovasculature and improve the mobility of patients with PAD with intermittent claudication. Thirty-eight patients (mean age 65 years; 71% male) with symptomatic PAD (confirmed by ankle-brachial index) were randomized 1:1 to receive canakinumab (150 mg subcutaneously) or placebo monthly for up to 12 months. The mean vessel wall area (by 3.0 T black-blood magnetic resonance imaging (MRI)) of the superficial femoral artery (SFA) was used to measure plaque volume. Mobility was assessed using the 6-minute walk test. Canakinumab was safe and well tolerated. Markers of systemic inflammation (interleukin-6 and high-sensitivity C-reactive protein) fell as early as 1 month after treatment. MRI (32 patients at 3 months; 21 patients at 12 months) showed no evidence of plaque progression in the SFA in either placebo-treated or canakinumab-treated patients. Although an exploratory endpoint, placebo-adjusted maximum and pain-free walking distance (58 m) improved as early as 3 months after treatment with canakinumab when compared with placebo. Although canakinumab did not alter plaque progression in the SFA, there is an early signal that it may improve maximum and pain-free walking distance in patients with symptomatic PAD. Larger studies aimed at this endpoint will be required to definitively demonstrate this. ClinicalTrials.gov Identifier: NCT01731990.


Assuntos
Anti-Inflamatórios/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Claudicação Intermitente/tratamento farmacológico , Doença Arterial Periférica/tratamento farmacológico , Idoso , Anti-Inflamatórios/efeitos adversos , Anticorpos Monoclonais Humanizados/efeitos adversos , Biomarcadores/sangue , Método Duplo-Cego , Tolerância ao Exercício/efeitos dos fármacos , Feminino , Alemanha , Humanos , Mediadores da Inflamação/sangue , Claudicação Intermitente/sangue , Claudicação Intermitente/diagnóstico , Claudicação Intermitente/fisiopatologia , Jordânia , Masculino , Pessoa de Meia-Idade , Doença Arterial Periférica/sangue , Doença Arterial Periférica/diagnóstico , Doença Arterial Periférica/fisiopatologia , Estudo de Prova de Conceito , Estudos Prospectivos , Recuperação de Função Fisiológica , Fatores de Tempo , Resultado do Tratamento , Estados Unidos
8.
Int J Mol Sci ; 20(15)2019 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-31344980

RESUMO

Heme oxygenase-1 (HO-1) is an intracellular enzyme that catalyzes the oxidation of heme to generate ferrous iron, carbon monoxide (CO), and biliverdin, which is subsequently converted to bilirubin. These products have anti-inflammatory, anti-oxidant, anti-apoptotic, and anti-thrombotic properties. Although HO-1 is expressed at low levels in most tissues under basal conditions, it is highly inducible in response to various pathophysiological stresses/stimuli. HO-1 induction is thus thought to be an adaptive defense system that functions to protect cells and tissues against injury in many disease settings. In atherosclerosis, HO-1 may play a protective role against the progression of atherosclerosis, mainly due to the degradation of pro-oxidant heme, the generation of anti-oxidants biliverdin and bilirubin and the production of vasodilator CO. In animal models, a lack of HO-1 was shown to accelerate atherosclerosis, whereas HO-1 induction reduced atherosclerosis. It was also reported that HO-1 induction improved the cardiac function and postinfarction survival in animal models of heart failure or myocardial infarction. Recently, we and others examined blood HO-1 levels in patients with atherosclerotic diseases, e.g., coronary artery disease (CAD) and peripheral artery disease (PAD). Taken together, these findings to date support the notion that HO-1 plays a protective role against the progression of atherosclerotic diseases. This review summarizes the roles of HO-1 in atherosclerosis and focuses on the clinical studies that examined the relationships between HO-1 levels and atherosclerotic diseases.


Assuntos
Aterosclerose/genética , Doença da Artéria Coronariana/genética , Heme Oxigenase-1/genética , Doença Arterial Periférica/genética , Animais , Aterosclerose/sangue , Aterosclerose/patologia , Aterosclerose/prevenção & controle , Biliverdina/metabolismo , Monóxido de Carbono/metabolismo , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/patologia , Doença da Artéria Coronariana/prevenção & controle , Heme/metabolismo , Heme Oxigenase-1/uso terapêutico , Humanos , Ferro/metabolismo , Doença Arterial Periférica/sangue , Doença Arterial Periférica/patologia , Doença Arterial Periférica/prevenção & controle , Espécies Reativas de Oxigênio/metabolismo
9.
Medicina (Kaunas) ; 55(7)2019 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-31336615

RESUMO

Background and objectives: Both in the pathogenesis of type 2 diabetes (DM 2) and Peripheral Arterial Disease (PAD), a vital role is played by endothelial dysfunction. Metabolic disorders found in DM 2 (hyperglycemia, insulin resistance), endothelial dysfunction, and increased inflammation lead to intensified atherothrombosis. The fibrinolysis system comprises a natural compensatory mechanism in case of hypercoagulability. The aim of this study was to assess concentrations of selected fibrinolysis parameters in the blood of patients with symptomatic PAD, including in particular concurrent DM 2 and other cardiovascular factors. Materials and Methods: In the group of 80 patients with PAD (27 F/53 M) and 30 healthy volunteers (10 F/20 M), the following parameters were measured: Concentrations of fibrinogen, tissue-Plasminogen Activator (t-PA Ag), Plasminogen Activator Inhibitor-1 (PAI-1 Ag), D-dimer, and platelet (PLT) count. Results: In the blood of patients with PAD and concomitant DM 2 significantly higher concentrations of fibrinogen were found in comparison with patients with PAD and without diabetes (p = 0.044). No significant impact was observed in individuals with atherosclerotic complications (manifested by coronary artery disease, atherosclerosis of cerebral arteries) and selected cardiovascular risk factors (smoking, LDL and triglyceride concentrations, BP values) on the levels of t-PA, PAI-1, D-dimer, and PLT count. It was found that t-PA Ag and PAI-1 Ag values tended to rise along with a BMI increase in the subgroups of subjects (with normal body mass, overweight, and obesity), but no statistically significant differences were observed. However, two significant positive correlations were reported between t-PA Ag and BMI, as well as between PAI-1 Ag and BMI. Conclusions: Type 2 diabetes in peripheral arterial disease affects the concentration of fibrinogen causing its increase, which is connected with the inflammation and prothrombotic process in the course of both conditions. The concurrence of atherosclerosis of coronary or cerebral arteries, smoking, LDL and TG concentrations, and BP value do not have a significant impact on the levels of analyzed fibrinolysis parameters. A positive correlation between BMI and t-PA Ag and PAI-1 Ag concentrations needs to be supported in further studies on a larger number of overweight and obese patients.


Assuntos
Síndrome Coronariana Aguda/sangue , Afibrinogenemia/sangue , Diabetes Mellitus Tipo 2/sangue , Fibrinogênio/análise , Doença Arterial Periférica/sangue , Síndrome Coronariana Aguda/complicações , Afibrinogenemia/complicações , Idoso , Diabetes Mellitus Tipo 2/complicações , Ensaio de Imunoadsorção Enzimática/métodos , Feminino , Fibrinólise/fisiologia , Voluntários Saudáveis/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Doença Arterial Periférica/etiologia , Inibidor 1 de Ativador de Plasminogênio/análise , Inibidor 1 de Ativador de Plasminogênio/sangue , Fatores de Risco , Ativador de Plasminogênio Tecidual/análise , Ativador de Plasminogênio Tecidual/sangue
10.
Ann Vasc Surg ; 60: 165-170, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31195106

RESUMO

BACKGROUND: Atherosclerosis is known to result in individuals with arterial stenosis or occlusion. Alternatively, certain atherosclerotic arteries develop aneurysms. However, there has been no clear explanation regarding the mechanism associated with this alternate clinical presentation. This study aimed to investigate the clinical and hematologic factors that could lead to the development of the different clinical outcomes of stenosis and aneurysm in atherosclerotic arterial disease. METHODS: From March 2016 to January 2018, 219 consecutive atherosclerotic patients, of whom 195 (171 men, 24 women) had stenosis or occlusion and 24 (19 men, 5 women) had aneurysm, were investigated. All patients underwent vascular procedures. Continuous variables studied were age, body mass index, smoking status (pack-years), frequency of alcohol consumption (days), levels of natural anticoagulants (protein C, protein S, and antithrombin III), coagulation-enhancing factors (factor VIII, fibrinogen, and homocysteine), antiphospholipid antibodies (lupus anticoagulant, immunoglobulin [Ig] G/IgM anticardiolipin antibody, and IgG/IgM anti-beta 2 glycoprotein I [anti-ß2GPI]), lipids (total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglyceride), and hemoglobin A1c. The investigated nominal variables were sex, diabetes mellitus, and hypertension. RESULTS: A logistic regression analysis of all nominal and continuous variables as independent variables revealed that IgM anticardiolipin antibody was a significant independent factor associated with aneurysm formation in atherosclerotic arterial disease (P = 0.042). CONCLUSIONS: A higher IgM anticardiolipin antibody level may be one of the causative factors behind aneurysm development and may have the clinical potential to be used as a biomarker to predict the development of aneurysms in atherosclerotic arterial disease.


Assuntos
Aneurisma/etiologia , Anticorpos Anticardiolipina/sangue , Imunoglobulina M/sangue , Doença Arterial Periférica/complicações , Idoso , Aneurisma/sangue , Aneurisma/diagnóstico , Aneurisma/terapia , Biomarcadores/sangue , Constrição Patológica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença Arterial Periférica/sangue , Doença Arterial Periférica/diagnóstico , Doença Arterial Periférica/terapia , Prognóstico , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Regulação para Cima
11.
Cardiovasc Diabetol ; 18(1): 74, 2019 06 05.
Artigo em Inglês | MEDLINE | ID: mdl-31167666

RESUMO

BACKGROUND: Type-2 diabetes mellitus is one of the major risk factors of atherosclerosis, particularly in peripheral artery disease (PAD). Several studies have documented a correlation between omentin-1 serum levels, atherosclerosis, and cardiovascular diseases. However, a clear link between circulating omentin-1 and PAD in diabetic patients has yet to be established. The aim of this study was to investigate the potential role of omentin-1 in PAD in type-2 diabetic patients. METHODS: In this cross-sectional study, we analyzed omentin-1 serum levels by ELISA in 600 type-2 diabetic patients with (n = 300) and without (n = 300) PAD at Fontaine's stage II, III, or IV. RESULTS: We found that omentin-1 serum levels were significantly lower in diabetic patients with PAD than in diabetic controls (29.46 vs 49.24 ng/mL, P < 0.001) and that the levels gradually decreased in proportion to disease severity (P < 0.05). The association between omentin-1 levels and PAD remained significant after adjusting for major risk factors in a multivariate analysis. CONCLUSIONS: Our results suggest that omentin-1 is reduced in type 2 diabetic patients with PAD and that omentin-1 levels are related to disease severity.


Assuntos
Citocinas/sangue , Diabetes Mellitus Tipo 2/sangue , Angiopatias Diabéticas/sangue , Lectinas/sangue , Doença Arterial Periférica/sangue , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Estudos de Casos e Controles , Estudos Transversais , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico , Angiopatias Diabéticas/diagnóstico , Angiopatias Diabéticas/etiologia , Regulação para Baixo , Feminino , Proteínas Ligadas por GPI/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Doença Arterial Periférica/diagnóstico , Doença Arterial Periférica/etiologia , Índice de Gravidade de Doença
12.
Biomarkers ; 24(6): 615-621, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31215249

RESUMO

Purpose: The aim of this study is to evaluate plasma biomarkers as predictors for peripheral arterial disease (PAD). Materials and methods: Prospective longitudinal cohort study of middle-aged individuals from the cardiovascular cohort of the Malmö Diet and Cancer study (MDCS) (n = 5550; 1991-94). Cystatin C, copeptin, N-terminal pro-B-type natriuretic peptide (N-BNP), midregional proatrial natriuretic peptide (MR-proANP), mid-regional proadrenomedullin (MR-proADM), and conventional risk factors were measured at baseline. The diagnosis of symptomatic PAD was validated in 97% of the cases. Results: Cumulative incidence of PAD during median follow up of 23.4 years was 4.4% (men 5.9%, women 3.3%). Adjusted for age, sex, smoking, body mass index, hypertension, diabetes mellitus and total cholesterol, copeptin (hazard ratio [HR] 1.46; 95% confidence interval [CI] 1.19-1.80), N-BNP (HR 1.28; 95% CI 1.11-1.48), and cystatin C (HR 1.19; 95% CI 1.10-1.29) were independently associated with incident PAD. Subjects with the three biomarkers copeptin, N-BNP, and cystatin C in the highest quartiles, ran a high risk of incident PAD (HR 3.29; 95% CI 1.76-6.17) compared to those with no biomarker in the highest quartile. Conclusion: Copeptin, N-BNP, and cystatin C were associated with incident symptomatic PAD, implying that these biomarkers are sensitive indicators of early subclinical PAD. Clinical significance First prospective longitudinal cohort study evaluating Cystatin C, copeptin, N-terminal pro-B-type natriuretic peptide (N-BNP), midregional proatrial natriuretic peptide (MR-proANP), and mid-regional proadrenomedullin (MR-proADM) as predictors for peripheral arterial disease (PAD). Copeptin, N-BNP, and Cystatin C where independently associated with incident symptomatic PAD after adjustment for conventional risk factors. Copeptin, N-BNP, and Cystatin C seem to be sensitive indicators of early subclinical PAD.


Assuntos
Cistatina C/sangue , Glicopeptídeos/sangue , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Doença Arterial Periférica/diagnóstico , Adrenomedulina/sangue , Idoso , Fator Natriurético Atrial/sangue , Biomarcadores/sangue , Colesterol/sangue , Diabetes Mellitus/fisiopatologia , Feminino , Humanos , Hipertensão/fisiopatologia , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Doença Arterial Periférica/sangue , Doença Arterial Periférica/epidemiologia , Doença Arterial Periférica/fisiopatologia , Estudos Prospectivos , Precursores de Proteínas/sangue , Fatores de Risco , Fatores Sexuais , Fumar/fisiopatologia , Suécia/epidemiologia
13.
Cardiovasc Diabetol ; 18(1): 77, 2019 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-31174526

RESUMO

BACKGROUND: Microvascular blood flow (MBF) impairment in patients with lower extremity arterial disease (LEAD) is associated with more severe major adverse limb events (MALE). The contribution of ticagrelor, a P2Y12 antagonist and an adenosine enhancer, on blood viscosity (BV) and BV-dependent MBF in LEAD is unknown. The aim of the trial is to investigate the effects of ticagrelor on BV, and explore the association of BV-dependent MBF in participants with LEAD and type 2 diabetes (T2DM). METHODS: Randomized, double-blind, double-dummy, crossover trial design that compares treatment with aspirin 81 mg/ticagrelor placebo, aspirin 81 mg/ticagrelor 90 mg twice daily and aspirin placebo/ticagrelor 90 mg twice daily on high-shear (300 s-1) and low-shear (5 s-1) BV, and laser Doppler flowmetry (LDF) in the dorsum of the feet of participants with T2DM. RESULTS: We randomized 70 (45% female) participants aged (mean ± SD) 72 ± 9 years. The duration of LEAD was 12.3 ± 10.3 years, and 96.9% reported intermittent claudication symptoms. Use of statins was 93% (high-intensity 43%, moderate intensity 49%), renin-angiotensin-aldosterone system inhibitors (75%) and beta-blockers (61%). Treatment with ticagrelor with or without aspirin reduced high-shear BV by 5%, in both cases, while aspirin monotherapy increased high-shear BV by 3.4% (p < 0.0001). Ticagrelor with or without aspirin reduced low-shear BV by 14.2% and 13.9% respectively, while aspirin monotherapy increased low-shear BV by 9.3% (p < 0.0001). The combination of ticagrelor and aspirin increased MBF in the left foot compared to the other two treatments (p = 0.02), but not in the right foot (p = 0.25). CONCLUSIONS: Ticagrelor should be considered in the treatment of microvascular disease in patients with LEAD and T2DM. Trial registration Registration number: NCT02325466, registration date: December 25, 2014.


Assuntos
Viscosidade Sanguínea/efeitos dos fármacos , Diabetes Mellitus Tipo 2/complicações , Extremidade Inferior/irrigação sanguínea , Microcirculação/efeitos dos fármacos , Doença Arterial Periférica/tratamento farmacológico , Inibidores da Agregação de Plaquetas/uso terapêutico , Ticagrelor/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Velocidade do Fluxo Sanguíneo , Estudos Cross-Over , Diabetes Mellitus Tipo 2/sangue , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cidade de Nova Iorque , Doença Arterial Periférica/sangue , Doença Arterial Periférica/complicações , Doença Arterial Periférica/fisiopatologia , Inibidores da Agregação de Plaquetas/efeitos adversos , Fluxo Sanguíneo Regional , Ticagrelor/efeitos adversos , Fatores de Tempo , Resultado do Tratamento
14.
Ann Vasc Surg ; 60: 286-292, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31075466

RESUMO

BACKGROUND: The objective of this clinical study was to investigate the anticoagulant effect of standard fixed dose of heparin during endovascular intervention in the lower extremity arteries. METHODS: A prospective clinical pilot study was completed with retrospective quality review of patients between 2015 and 2017 (n = 61). Patients undergoing elective endovascular intervention for arterial insufficiency in the lower extremities were enrolled. A standard fixed intra-arterial dose of 5000 IU of unfractionated heparin (UFH) was administered during the procedure without adjustment for weight or monitoring. Activated clotting time (ACT) was measured before and ten minutes after heparin administration and at the end of the procedure. The primary study end point was the level of heparin anticoagulation after standard perioperative administration. RESULTS: Mean age was 74 ± 9 years, 48% women. Mean weight was 74 ± 15 kg, and mean BMI, 25.6 ± 4.7 kg/m2. The endovascular interventions were performed at the iliac arteries 19.7% (12/61), at the femoral popliteal segment 50.8 % (31/61), below the knee arteries 6.6% (4/61), and at multiple levels 13% (8/61). The perioperative mean ACT increased from baseline 155 ± 43 s (n = 31) to ten minutes after heparin administration 290 ± 70 s (n = 60) (P < 0.01) and was at the end of the procedure 276 ± 73 s (n = 59). Perioperative ACT ten minutes after heparin administration: 5.0% (3/60) of the patients had ACT <200 s, 25.0% (15/60) had ACT 200-250 s, 48.3% (29/60) ACT 251-349, and 21.7% (13/60) ACT ≥350 s. At the end of the procedure, 17.2 % (10/58) of the patients had ACT <200, 24.1 % (14/58) had ACT 200-250 s, 37.9% (22/58) ACT 251-349, and 20.7 % (12/58) ACT ≥350 s. The mean dose of heparin per kg body weight was 70 ± 15 IU/kg. There was a significant difference between the ACT groups when analyzing heparin dose per kg body weight: 54 ± 14 IU/kg for patients with ACT <200, 69 ± 13 IU/kg with ACT 200-250 s, 68 ± 13 IU/kg with ACT 251-349, and 81 ± 18 IU/kg with ACT >350 (P = 0.0095). The same pattern was seen for heparin dose per BMI and DuBois. In univariate logistic regression analysis, ACT ≥350 s was associated with lower body weight (OR 0.92; 95% CI 0.87-0.98; P = 0.008), lower BMI (OR 0.80; 95% CI 0.67-0.96; P = 0.014), and lower body surface area DuBois (OR 0.53; 95% 0.32-0.85; P = 0.009). In multivariable regression, the ACT association with body weight remained (OR 0.92; 95% 0.87-0.98; P = 0.008). There were no perioperative or immediate postoperative bleeding complications requiring blood transfusion or surgical intervention in this study cohort. CONCLUSIONS: The standard heparin dosing of 5000 IU during endovascular intervention for arterial insufficiency in the lower extremities helps achieve ACT >200 s in almost all patients, but most patients were outside recommended target interval. To provide a more consistent and predictable heparinization, a weight-based bolus dose of 70 IU heparin/kg is recommended.


Assuntos
Anticoagulantes/administração & dosagem , Coagulação Sanguínea/efeitos dos fármacos , Procedimentos Endovasculares , Heparina/administração & dosagem , Extremidade Inferior/irrigação sanguínea , Doença Arterial Periférica/terapia , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/efeitos adversos , Monitoramento de Medicamentos/métodos , Procedimentos Endovasculares/efeitos adversos , Feminino , Heparina/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Doença Arterial Periférica/sangue , Doença Arterial Periférica/diagnóstico , Projetos Piloto , Estudos Prospectivos , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Tempo de Coagulação do Sangue Total
15.
Biofactors ; 45(4): 507-516, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31145514

RESUMO

The red blood cell distribution width (RDW) is an index of the heterogeneity of circulating red blood cell size, which along with other standard complete blood count (CBC) parameters are used to identify hematological system diseases. Besides hematological disorders, several clinical studies have shown that an increased in the RDW may be associated with other diseases including acute pancreatitis, chronic kidney disease, gastrointestinal disorders, cancer, and of special interest in this review, cardiovascular disease (CVD). The diagnostic and prognostic value of RDW in different CVD (acute coronary syndrome, ischemic cerebrovascular disease, peripheral artery disease, atrial fibrillation, heart failure, and acute ischemic stroke) has been reviewed in this article, to provide an understanding how its measurement may be applied to improve the management of these conditions.


Assuntos
Síndrome Coronariana Aguda/diagnóstico , Fibrilação Atrial/diagnóstico , Isquemia Encefálica/diagnóstico , Eritrócitos/patologia , Insuficiência Cardíaca/diagnóstico , Doença Arterial Periférica/diagnóstico , Acidente Vascular Cerebral/diagnóstico , Síndrome Coronariana Aguda/sangue , Fibrilação Atrial/sangue , Biomarcadores/sangue , Isquemia Encefálica/sangue , Índices de Eritrócitos , Insuficiência Cardíaca/sangue , Humanos , Doença Arterial Periférica/sangue , Valor Preditivo dos Testes , Prognóstico , Acidente Vascular Cerebral/sangue
16.
Nutr Metab Cardiovasc Dis ; 29(8): 815-821, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31133497

RESUMO

BACKGROUND AND AIM: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is rapidly gaining attention as a potential risk of developing atherosclerosis due to its crucial role in the regulation of low-density lipoprotein cholesterol (LDL-C) metabolism. The present study investigated the relationship between serum PCSK9 levels and early atherosclerosis as assessed by carotid intimal-medial thickness (CIMT) and brachial-ankle pulse wave velocity (ba-PWV) in newly diagnosed type 2 diabetes mellitus (T2DM). METHODS AND RESULTS: A total of 100 newly diagnosed T2DM were enrolled and further divided into the thickened CIMT group (n = 41) and the non-thickened CIMT group (n = 59) according to the results of color Doppler ultrasonography. Serum PCSK9 levels, CIMT, ba-PWV, and metabolic parameters were measured. Patients in the thickened CIMT group had higher serum PCSK9 levels than patients in the non-thickened CIMT group (all P < 0.05). CIMT and ba-PWV were both positively correlated to serum PCSK9 levels, while serum PCSK9 levels were positively correlated to white blood cell count, neutrophil, lymphocyte, and high-sensitivity C-reactive protein (P < 0.05). Multiple linear regression indicated that serum PCSK9 level was an independent predictor of CIMT (ß = 0.637, P < 0.001) and ba-PWV (ß = 0.600, P < 0.001). Binary logistic regression analysis showed that serum PCSK9 levels were independent risk factors of thickened CIMT [OR = 1.120, 95%CI (1.041-1.204), P = 0.002]. CONCLUSION: Serum PCSK9 levels are significantly correlated with CIMT and ba-PWV, independent of CAD risk factors. Therefore, serum PCSK9 level may have the potential to serve as a prescriptive biomarker for early arteriosclerosis in newly diagnosed T2DM.


Assuntos
Doenças das Artérias Carótidas/sangue , Diabetes Mellitus Tipo 2/sangue , Angiopatias Diabéticas/sangue , Doença Arterial Periférica/sangue , Pró-Proteína Convertase 9/sangue , Idoso , Índice Tornozelo-Braço , Biomarcadores/sangue , Doenças das Artérias Carótidas/diagnóstico por imagem , Doenças das Artérias Carótidas/enzimologia , Doenças das Artérias Carótidas/etiologia , Espessura Intima-Media Carotídea , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/enzimologia , Angiopatias Diabéticas/diagnóstico por imagem , Angiopatias Diabéticas/enzimologia , Angiopatias Diabéticas/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença Arterial Periférica/diagnóstico , Doença Arterial Periférica/enzimologia , Doença Arterial Periférica/etiologia , Valor Preditivo dos Testes , Fatores de Risco , Ultrassonografia Doppler em Cores , Regulação para Cima
17.
Diab Vasc Dis Res ; 16(5): 483-485, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31064218

RESUMO

Carboxymethyl-lysine is an advanced glycation end product that is detectable in the serum. Higher carboxymethyl-lysine levels have been associated with increased risk of coronary heart disease, stroke and cardiovascular mortality. We determined whether high carboxymethyl-lysine levels are also associated with the risk of peripheral artery disease in Cardiovascular Health Study participants who were all aged 65 years and older at baseline. Multivariate Cox proportional hazards models were used to determine the association of baseline carboxymethyl-lysine levels with incident peripheral artery disease in 3267 individuals followed for a median length of 10.0 years. A total of 157 cases of incident peripheral artery disease occurred during follow-up. No significant relationship between carboxymethyl-lysine and risk of peripheral artery disease was found (hazard ratio per standard deviation increment = 1.03; 95% confidence interval = 0.87, 1.23).


Assuntos
Produtos Finais de Glicação Avançada/sangue , Lisina/análogos & derivados , Doença Arterial Periférica/sangue , Doença Arterial Periférica/epidemiologia , Idoso , Biomarcadores/sangue , Feminino , Humanos , Incidência , Lisina/sangue , Masculino , Doença Arterial Periférica/diagnóstico , Prognóstico , Medição de Risco , Fatores de Risco , Fatores de Tempo , Estados Unidos/epidemiologia
18.
Mol Med Rep ; 19(6): 5195-5202, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31059098

RESUMO

MicroRNAs (miRNAs) are considered to be critical mediators of gene expression with respect to tumor progression, although their role in ischemia­induced angiogenesis is poorly characterized, including in peripheral arterial disease (PAD). Furthermore, the underlying mechanism of action of specific miRNAs in PAD remains unknown. Reverse transcription­quantitative polymerase chain reaction analysis revealed that microRNA­93 (miR­93) was significantly upregulated in patients with PAD and in the EA.hy926 endothelial cells in response to hypoxia. Additionally, miRNA (miR)­93 promoted angiogenesis by enhancing proliferation, migration and tube formation. Cyclin dependent kinase inhibitor 1A (CDKN1A), verified as a potential target gene of miR­93, was inhibited by overexpressed miR­93 at the protein and mRNA expression levels. Furthermore, a hind­limb ischemia model served to evaluate the role of miR­93 in angiogenesis in vivo, and the results demonstrated that miR­93 overexpression enhanced capillary density and perfusion recovery from hind­limb ischemia. Taken together, miR­93 was indicated to be a promising target for pharmacological regulation to promote angiogenesis, and the miR­93/CDKN1A pathway may function as a novel therapeutic approach in PAD.


Assuntos
Inibidor de Quinase Dependente de Ciclina p21/metabolismo , MicroRNAs/metabolismo , Neovascularização Fisiológica , Doença Arterial Periférica/patologia , Regiões 3' não Traduzidas , Idoso , Animais , Hipóxia Celular , Linhagem Celular , Proliferação de Células , Inibidor de Quinase Dependente de Ciclina p21/química , Inibidor de Quinase Dependente de Ciclina p21/genética , Modelos Animais de Doenças , Células Endoteliais/citologia , Células Endoteliais/metabolismo , Feminino , Membro Posterior/patologia , Humanos , Isquemia/metabolismo , Isquemia/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/química , MicroRNAs/genética , Pessoa de Meia-Idade , Doença Arterial Periférica/sangue , Doença Arterial Periférica/genética
19.
Clin Chim Acta ; 495: 215-220, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30981846

RESUMO

BACKGROUND: Peripheral artery disease (PAD) becomes more prevalent with advancing age and is associated with elevated risk of cardiovascular events and shortened life expectancy. We investigated the prognostic performance of cardiac and vascular biomarkers in a cohort of PAD patients. METHODS: A total of 95 PAD patients were enrolled (mean age 68 years, range 47 to 86 years, 73 males). Carotid intima-media thickness (cIMT), ankle brachial index (ABI), high sensitive cardiac troponin T, and N-terminal pro-B-type Natriuretic Peptide (NT-proBNP) were measured. RESULTS: During a median follow-up time of 9.5 years, 44 patients died and 51 patients survived. Upon Kaplan-Meier survival analysis hs-TnT (P < .001) or NT-proBNP levels (P < .001) above the median but not cIMT above the median (P = .488) or ABI below the median (P < .436)were associated with reduced survival rate. Upon univariate cox regression and after adjustment for age, gender, prior cerebral artery disease, and diabetes mellitus only the association between hs-cTnT and mortality remained significant (HR 1.93, 95% CI 1.33-2.79, P < .001). In receiver operating curve analysis hs-cTnT (area under the curve [AUC]: 0.77, 95% CI: 0.67-0.87, P < .001) NT-proBNP (AUC: 0.74, 95% CI: 0.64-0.84, P < .001) as well as hs-cTnT, and NT-proBNP combined (AUC: 0.79, 95% CI: 0.69-0.88, P < .001) were superior to cIMT (AUC: 0.64, 95%, CI: 0.53-0.76, P = .022) and ABI (AUC: 0.57, 95% CI: 0.44-0.68, P = .313) in discriminating risk for mortality. CONCLUSION: hs-cTnT and NT-proBNP should be taken into account for prognosis of patients with PAD.


Assuntos
Miocárdio/metabolismo , Doença Arterial Periférica/diagnóstico , Doença Arterial Periférica/mortalidade , Idoso , Idoso de 80 Anos ou mais , Índice Tornozelo-Braço , Aterosclerose/complicações , Biomarcadores/sangue , Espessura Intima-Media Carotídea , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Doença Arterial Periférica/sangue , Doença Arterial Periférica/complicações , Prognóstico
20.
Angiology ; 70(8): 737-746, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31030528

RESUMO

GlycA, a composite biomarker of systemic inflammation, is associated with cardiovascular disease (CVD) and mortality, but its relationship with peripheral artery disease (PAD) is unknown. We assessed whether plasma GlycA is associated with ankle-brachial index (ABI), carotid plaque (CP), and incident clinical PAD among 6466 Multi-Ethnic Study of Atherosclerosis participants without CVD at baseline. GlycA, ABI, and CP were measured at baseline. Both ABI and CP were remeasured at 10 years. Incident clinical PAD was ascertained from hospital records. We used logistic, Cox, and linear mixed regression models adjusted for demographic and lifestyle factors. Mean (standard deviation, SD) was 62 (10) years for age and 381 (61) µmol/L for GlycA; 53% were women. GlycA was associated with both prevalent low ABI ≤0.8 (prevalence odds ratio [95% confidence interval, CI] per SD increment in GlycA, 1.65 [1.39-1.97]) and CP (1.19 [1.11-1.27]) at baseline. There were no significant associations of GlycA with incident low ABI, incident CP, or 10-year change in ABI or CP score. We identified 110 incident cases of PAD after 79 590 person-years. The hazard ratio (95% CI) of incident PAD per SD increment in GlycA was 1.38 (1.14-1.66). In conclusion, GlycA was associated with prevalent low ABI, prevalent CP, and incident PAD after a median of 14 years.


Assuntos
Aterosclerose/sangue , Biomarcadores/sangue , Inflamação/sangue , Doença Arterial Periférica/sangue , Idoso , Aterosclerose/diagnóstico , Aterosclerose/terapia , Feminino , Humanos , Inflamação/diagnóstico , Masculino , Pessoa de Meia-Idade , Doença Arterial Periférica/diagnóstico , Placa Aterosclerótica/sangue , Placa Aterosclerótica/diagnóstico , Modelos de Riscos Proporcionais , Medição de Risco , Fatores de Risco
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