Made available in DSpace on 2014-06-11T19:30:52Z (GMT). No. of bitstreams: 0 Previous issue date: 2006-12-15Bitstream added on 2014-06-13T20:00:57Z : No. of bitstreams: 1 venancio_ls_dr_botfm.pdf: 1176932 bytes, checksum: cb3091aa4e4bde7e6ddd7327173e8782 (MD5) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / Estudos epidemiológicos mostraram que a prevalência de doença arterial periférica (DAP) é alta e tem como fator etiológico principal a aterosclerose. Os fatores de risco para o desenvolvimento da aterosclerose são bastante conhecidos, e nos últimos anos, foi identificado, além destes, a homocisteína. Embora ainda não haja consenso sobre a dose exata e a forma de utilização, principalmente do folato na forma de suplementos, adequação alimentar, fortificação de cereais, para o tratamento da hiper-homocisteinemia, diversos estudos realizados em pacientes com doença vascular coronariana, cerebral e periférica, mostraram que o folato, isoladamente ou em combinação com a vitamina B6 e B12 pode reduzir as concentrações sanguíneas homocisteína e também diminuir a concentração de alguns marcadores de biológicos do processo de aterosclerose. No entanto, estudos recentes não comprovaram este benefício sobre o processo inflamatório associado à hiper-homocisteinemia. Portanto, a suplementação ou, a fortificação, ou a adequação dietética isolada do folato é uma terapêutica custoefetiva na prevenção e no controle da homocisteinemia, mas ainda persiste inconclusiva quanto ao impacto sobre a evolução das doenças vasculares. / Epidemiological studies have shown that the prevalence of peripheral arterial disease (PAD) is high and has atherosclorosis as its etiological factor. Risk factors for the development of atherosclerosis are widely known, and, for the past years, homocysteine has been identified as one of them. Although there is still no consensus as to the exact dose and manner of use, mainly of folate in the form of supplements, eating adjustment, cereal strengthening, for the treatment of hyperhomocysteinemia, several studies done in coronary, cerebral and peripheral vascular disease patients have shown that folate, isolatedly or in combination with vitamins B6 and B12, may reduce blood concentrations of homocysteine as well as the concentration of some biological markers in the process of atherosclerosis. However, recent studies have not corroborated this benefit for the inflammatory process associated with hyperhomocysteinemia. Consequently, supplementation, strengthening and diet adjustment devoid of folate are not cost-effective therapies in the prevention and control of homocysteine, but it is still inconclusive regarding the impact on the evolution of vascular diseases.

Research Objective Patients with chronic kidney disease (CKD) are at increased risk for atherosclerosis and peripheral artery disease (PAD). PAD has received far less attention than coronary artery disease (CAD) in CKD patients. Few studies have examined risk factors for PAD in CKD. We studied the possible related risk factors and benefit of hypertension treatment in CKD patients with PAD. Data Sources We included 129 patients of both sexes with stages 3 to 5 of CKD, as described by the Kidney Outcome Quality Initiatives (K/DOQI ) classification, without receiving dialysis therapy, not previously diagnosed with PAD. Study Design The following information were collected within six month period, including demographic characteristics, history of hypertension, anti-hypertension drug, diabetes, smoking, and pre-existing cardiovascular disease, body mass index (BMI), fasting blood glucose, HbA1c, total cholesterol, triglyceride(TG), high density lipoprotein cholesterol (HDL), low density lipoprotein cholesterol(LDL), calcium (Ca), phosphate(P), Albumin, uric acid, urine protein. Ankle-brachial index (ABI) is a noninvasive diagnostic test that is efficient in detecting asymptomatic PAD with ABI <0.9. Findings There were 22 (17.7 %) participants with PAD. Higher systolic blood pressure (SBP), higher diastolic blood pressure (DBP), higher pulse pressure showed strong association with PAD in CKD patients. On further analysis, significant fewer patients treated with calcium channel blocker (CCB) in hypertensive CKD patients with PAD (£q2 =7.055, p =0.008). The multivariate logistic regression analysis in hypertensive patients demonstrated the risk factors for PAD was pulse pressure, and Calcium channel blocker treatment may correlate with decreasing PAD formation (odds ratio= 0.232, 95% CI=0.07-0.73, p =0.013) in CKD patients. Conclusion There is a high prevalence rate of PAD in population of CKD, especially those with hypertension. ABI should be routinely examined in these patients who can benefit earlier from therapeutic measures.

Orientador: Winston Bonetti Yoshida / Banca: Paula Garcia Chiarello / Banca: Hamilton Almeida Rollo / Banca: Avany Fernandes Pereira / Banca: Newton de Barros Júnior / Resumo: Estudos epidemiológicos mostraram que a prevalência de doença arterial periférica (DAP) é alta e tem como fator etiológico principal a aterosclerose. Os fatores de risco para o desenvolvimento da aterosclerose são bastante conhecidos, e nos últimos anos, foi identificado, além destes, a homocisteína. Embora ainda não haja consenso sobre a dose exata e a forma de utilização, principalmente do folato na forma de suplementos, adequação alimentar, fortificação de cereais, para o tratamento da hiper-homocisteinemia, diversos estudos realizados em pacientes com doença vascular coronariana, cerebral e periférica, mostraram que o folato, isoladamente ou em combinação com a vitamina B6 e B12 pode reduzir as concentrações sanguíneas homocisteína e também diminuir a concentração de alguns marcadores de biológicos do processo de aterosclerose. No entanto, estudos recentes não comprovaram este benefício sobre o processo inflamatório associado à hiper-homocisteinemia. Portanto, a suplementação ou, a fortificação, ou a adequação dietética isolada do folato é uma terapêutica custoefetiva na prevenção e no controle da homocisteinemia, mas ainda persiste inconclusiva quanto ao impacto sobre a evolução das doenças vasculares. / Abstract: Epidemiological studies have shown that the prevalence of peripheral arterial disease (PAD) is high and has atherosclorosis as its etiological factor. Risk factors for the development of atherosclerosis are widely known, and, for the past years, homocysteine has been identified as one of them. Although there is still no consensus as to the exact dose and manner of use, mainly of folate in the form of supplements, eating adjustment, cereal strengthening, for the treatment of hyperhomocysteinemia, several studies done in coronary, cerebral and peripheral vascular disease patients have shown that folate, isolatedly or in combination with vitamins B6 and B12, may reduce blood concentrations of homocysteine as well as the concentration of some biological markers in the process of atherosclerosis. However, recent studies have not corroborated this benefit for the inflammatory process associated with hyperhomocysteinemia. Consequently, supplementation, strengthening and diet adjustment devoid of folate are not cost-effective therapies in the prevention and control of homocysteine, but it is still inconclusive regarding the impact on the evolution of vascular diseases. / Doutor

INTRODUÇÃO: A caminhada é recomendada no tratamento de pacientes com claudicação intermitente (CI) por aumentar a capacidade funcional. Porém, os efeitos cardiovasculares de uma sessão de caminhada foram pouco estudados nestes pacientes. OBJETIVO: Analisar o efeito de uma sessão de caminhada sobre a função e regulação cardiovascular pós-exercício de pacientes com CI. MATERIAS E MÉTODOS: 20 pacientes com CI participaram de duas sessões experimentais realizadas em ordem aleatória: Controle (repouso em pé por 60 minutos) e Exercício (15 séries de dois minutos de caminhada na frequência cardíaca (FC) do limiar de dor, intercaladas por dois minutos de recuperação passiva). Nas duas sessões, a pressão arterial (PA) clínica e de 24 horas, o débito cardíaco (DC - reinalação de CO2), o fluxo sanguíneo para os membros ativo e inativo (plestismografia de oclusão venosa), a capacidade vasodilatadora (hiperemia reativa) e a modulação autonômica cardiovascular (análise espectral da variabilidade da FC e da PA) foram medidas antes e após as intervenções. O volume sistólico (VS) e a resistência vascular (RV) sistêmica foram calculados. Os dados foram analisados pela ANOVA de dois fatores para amostras repetidas, post-hoc de Newman-Keuls e P<0,05. RESULTADOS: O exercício prévio reduziu a PA clínica (PA média = -7±2 mmHg, P<0,05), mas a PA ambulatorial não se modificou. Após o exercício, o VS e o DC diminuíram (-5,62±1,97ml e -0,05±0,13 l/min, P<0,05). A RV sistêmica não se elevou pós-exercício e o exercício prévio impediu o aumento da RV na região ativa e inativa, sem modificar a resposta vasodilatadora. O exercício impediu a redução da FC pós-intervenção, pois impediu o aumento da modulação vagal cardíaca. CONCLUSÃO: Uma única sessão de caminhada promoveu hipotensão pós-exercício (HPE) em pacientes com CI no ambiente clínico, mas este efeito não perdurou no período ambulatorial. A HPE ocorreu pelo efeito do exercício reduzindo o VS e o DC e, simultaneamente, impedindo o aumento da RV sistêmica / INTRODUCTION: Walking exercise (WE) is recommended for patients with intermittent claudication (IC) because it improves functional capacity. However, cardiovascular responses after one session of WE has been poor studied. OBJECTIVE: To analyze the post-effects of a WE session on cardiovascular function and regulation in patients with IC. METHODS: Twenty IC patients randomly underwent two experimental sessions: Control (rest on treadmill for 60 min) and Exercise (fifteen 2-min bouts of WE at the heart rate (HR) of the onset of claudication pain, interpolated with 2-min rest intervals). Before and after the interventions, clinic and ambulatory blood pressure (BP), cardiac output (CO, CO2 rebreathing), blood flow to active and inactive limbs (venous occlusion plethysmography), vasodilatory capacity (reactive hyperemia), cardiovascular autonomic modulation (spectral analysis of HR and BP) were measured in both experimental sessions. Stroke volume (SV) and systemic vascular resistance (VR) were calculated. Data was analyzed by a two-way ANOVA for repeated measures followed by Newman-Keuls post-hoc test, with P<0.05. RESULTS: WE significantly decreased clinic BP ( Mean BP = -7±2 mmHg, P<0.05), but ambulatory BP did not change. After exercise, SV (-5.62±1.97ml) and CO (-0.05±0.13 l/min) decreased (P<0.05), whereas systemic VR did not change. Moreover, previously exercise prevented the increase in VR in the inactive and active limbs without modifying vasodilatory response. Exercise abolished HR decrease after the intervention, because it blunted cardiac vagal modulation increase. CONCLUSION: WE session promoted post-exercise hypotension (PEH) in patients with IC in clinic condition. However, this effect of WE was not maintained during ambulatory period. PEH was promoted by an effect of previous exercise decreasing CO and SV, and simultaneously, preventing an increase in systemic VR

<p>Lower extremity peripheral artery disease (PAD) is an increasingly prevalent manifestation of atherosclerosis that substantially limits mobility and increases mortality. Few options currently exists for practical conservative treatment of individuals with PAD. We have previously demonstrated that lower limb heat therapy (HT) can improve leg blood flow and reduce systolic blood pressure in patient with lower extremity PAD. Using three unique clinical trials, we sought to test the hypothesis that repeated exposure to HT would improve walking tolerance and vascular function in patients with lower extremity PAD. In these trials, we have sought to examine the clinical efficacy of HT, the physiological mechanisms which may underpin changes in walking endurance in this population, and also the practicality of employing HT in a home-based setting. The primary finding from these trials was that daily application of leg HT improved walking endurance in patients with lower-extremity PAD. Furthermore, the treatment adherence rate was excellent (<96%) and was not associated with severe adverse events. The changes in walking tolerance were consistently not associated with positive changes in vascular function, suggesting an alternative mechanism should be examined in future studies. </p>

The global prevalence of peripheral artery disease (PAD) is estimated to be about 120 million, making up about 25.6% of the worldwide burden of cardiovascular diseases (CVD). In the United States (U.S.), the prevalence of PAD is about 7%, representing nearly 8 million adults. There is a higher prevalence of disease in Blacks and non-Hispanic Whites, with approximately 30% of Blacks and 20% of non-Hispanic Whites developing PAD in their lifetime. The strong risk factors associated with PAD include smoking, diabetes, hypertension, age, and male sex. Our study aimed to estimate the effects of obesity, alcohol abuse, renal failure, and hypertension on patients’ length of stay (LOS) among patients admitted with a diagnosis of PAD. Using the 2012 U.S. National Inpatient Sample database, we included 336,790 patients with PAD as a separate comorbidity during their index admission. Our main outcome variable was patients’ total length of stay (LOS) during the index admission. We categorized LOS < 1 into next day discharge (NDD) and LOS > 1 into non-NDD. Our predictor variables were hypertension, obesity, alcohol abuse and renal failure. We ran descriptive statistics to delineate the baseline characteristics of our sample population, and bivariate analysis with t-test and chi-square analysis. Multivariable logistic regression was used to estimate odds of non-NDD given our comorbidities; obesity, hypertension, alcohol abuse, renal failure while adjusting for age, race, and sex. We reported frequencies, p-values, and odd ratios (ORs) at a 95% significance level with alpha at 0.05. Of our final sample, 54.8% were males while 45.2% were females and the mean age of patients was 71.7 + 12.8. Hypertension, obesity, alcohol abuse and renal failure were present in 75%, 12%, 3.4%, and 30.9% of patients, respectively. Majority (75%) of the patients were white, while Black and Hispanic patients made up 13.3% and 7.1%, respectively. In our adjusted model, we found that patients with hypertension had 12% lower odds of non-NDD (OR = 0.88, CI= 0.86-0.90, P<0.0001) compared to those without hypertension, females had 20% increase in the odds of non-NDD compared to males (OR = 1.20, CI= 1.18-1.23, P<0.0001), patients with obesity, alcohol abuse and renal failure had 39%, 43% and 45% increase in odds of non-NDD compared to those without these comorbidities. (OR = 1.39, CI= 1.34-1.44, P<0.0001), (OR = 1.43, CI= 1.35-1.52, P<0.0001), (OR = 1.45, CI= 1.42-1.49, P<0.0001). Given the significant association between obesity, alcohol abuse, and renal failure with prolonged hospital stay in patients admitted to hospital with PAD, our study highlights the importance of adequate management of pre-existing patients' comorbidities. This is expected to improve overall length of stay and total healthcare utilization and costs, among patients with PAD.

O treinamento de caminhada (TC) é recomendado para o tratamento de indivíduos com claudicação intermitente (CI) porque melhora a capacidade de caminhada. Além disso, seria interessante que o TC também promovesse modificações benéficas no sistema cardiovascular, pois os eventos cardiovasculares são a principal causa de morte nestes indivíduos. No entanto, os efeitos cardiovasculares do TC em indivíduos com CI foi pouco estudado. Assim, o objetivo deste estudo foi verificar o efeito do TC sobre o risco, a função e a regulação cardiovasculares em indivíduos com CI. Quarenta e dois indivíduos com CI foram divididos de forma aleatória em 2 grupos: controle (GC, n=20, sessões de 30 min de alongamento) e treinamento de caminhada (GT, n=22, 15 séries de 2 min de caminhada em intensidade correspondente à frequência cardíaca (FC) do limiar de dor intercalados por 2 min de repouso passivo). Nos dois grupos, a intervenção foi realizada 2 vezes/semana durante 12 semanas consecutivas. No início e ao final do estudo, os indivíduos realizaram as seguintes avaliações: glicemia e perfil lipídico de jejum; índice de massa corporal; capacidade de caminhada; consumo de oxigênio no 1º estágio e no pico do teste de esforço; índice tornozelo-braço (ITB) de repouso; janela isquêmica após teste ergoespirométrico; pressão arterial (PA) em repouso (auscultatória) e de 24 horas (oscilométrica); débito cardíaco (DC - reinalação de CO2); FC (ECG); volume sistólico (VS); resistência vascular (RV) sistêmica, do antebraço e da perna (plestismografia); componentes de alta (AF) e baixa (BF) frequência da variabilidade da FC; e sensibilidade barorreflexa espontânea (SBR). Mudanças significantes (P<0,05) ao longo do tempo e entre os grupos foram verificadas pela análise de variância ANOVA de dois fatores para medidas repetidas. O TC aumentou significantemente a capacidade de caminhada (&Delta;=+302±85m) e a SBR (&Delta;=+2.13±1.07 ms/mmHg), e diminuiu o VO2) no 1º estágio do teste (&Delta;=-1,8±0,4ml.kg-1.min-1), a janela isquêmica (&Delta;=- 0,40±0,38mmHg.min.m-1), a PA média (&Delta;=-5±2mmHg), a variabilidade da PA média de 24h (&Delta;=-0,8±0,2mmHg), o DC (&Delta;=-0.37±0.24L/min), a FC (&Delta;=- 4±2bpm), a RV do antebraço (&Delta;=-8.5±2.8 U) e a razão BF/AF (&Delta;=-1.24±0.99). A glicemia, o perfil lipídico, o índice de massa corporal, o VO2) pico, o ITB de repouso e a RV sistêmica e da perna não foram modificadas pelo TC. Não houve mudança em nenhuma variável no GC. Em conclusão, o TC melhorou a capacidade de caminhada, a economia de caminhada e a janela isquêmica. Além disso, o TC melhorou a função (PA, DC, FC e RV antebraço) e a regulação (BF/AF e SBR) cardiovasculares em indivíduos com CI. Estas alterações fornecem suporte adicional para a utilização do TC no tratamento de indivíduos com CI / Walking training (WT) is recommended for the treatment of patients with intermittent claudication (IC) because it improves walking capacity. Moreover, it would be interesting that WT also promotes beneficial changes on cardiovascular system, since cardiovascular events are the main causes of death in these patients. Nevertheless, the effects of WT on cardiovascular system in patients with IC have been poorly studied. Thus, the objective of this study was to investigate the effects of WT on cardiovascular risk, function and regulation in patients with IC. Forty-two IC patients were randomly divided into 2 groups: Control (CG, n=20, 30 min of stretching exercises) and walking training (TG, n=22, 15 sets of 2:2-min walk:rest at the heart rate (HR) of pain threshold). In both groups, the intervention was performed twice/week for 12 consecutive weeks. At the beginning and end of the study, the following measured were done: fasting glycemia and lipid profile; body mass index; walking capacity; VO2 at the first stage and the peak of a treadmill test; ankle brachial index (ABI); ischemic window after maximal test; resting (auscultatory) and 24-hour (oscillometric) blood pressure (BP); cardiac output (CO - CO2 rebreathing); heart rate (HR - ECG); stroke volume (SV); systemic, forearm and leg vascular resistance (VR - plethysmography); low- (LF) and high-frequency (HF) components of HR variability; and spontaneous baroreflex sensitivity (SBS). Significant changes (P<0.05) over time and between groups were assessed by 2-way ANOVA for repeated measures. WT significantly increased walking capacity (&Delta;=+302±85m) and SBS (&Delta;=+2.13±1.07 ms/mmHg), and decreased VO2 at the first stage of treadmill test (&Delta;=-1.8±0.4ml.kg-1.min-1), ischemic window (&Delta;=-0.40±0.38mmHg.min.m-1), mean BP (&Delta;=-5±2mmHg), ambulatory mean BP variability (&Delta;=-0,8±0,2 mmHg), CO (&Delta;=-0.37±0.24 L/min), HR (&Delta;=- 4±2bpm), forearm VR (&Delta;=-8.5±2.8 U) and LF/HF (&Delta;=-1.24±0.99). Glycemia, lipid profile, body mass index, VO2 peak, ABI, systemic and leg VR were unchanged following WT. There was no significant change for any variable in CG. In conclusion, WT enhanced walking capacity, walking economy and ischemic window. In addition, WT improved cardiovascular function (BP, CO, HR and forearm VR) and autonomic regulation (LF/HF, SBS) in patients with IC. These changes provide further support for the use of regular WT in treating patients with IC

Made available in DSpace on 2016-01-26T12:51:48Z (GMT). No. of bitstreams: 1 luiscesarfavaspessoto_tese.pdf: 1404885 bytes, checksum: 6230d115074147a6fe745e2f09efdcd4 (MD5) Previous issue date: 2012-08-09 / Introduction: The assessment of erectile dysfunction (ED) as an early symptom of endothelial dysfunction and atherosclerosis may be important to the identification of patients at high cardiovascular risk. Objective: The aim of the present study was to investigate the influence of systemic arterial hypertension (SAH) and peripheral artery disease (PAD) in patients with ED. Patients and Methods: One hundred twenty-five patients with ED (mean age: 59.82 ± 10.48 years; range 19 to 88), regardless of race, from the region of São José do Rio Preto, state of São Paulo, Brazil were evaluated between March and October 2011. ED was classified as mild (Grade 1), moderate (Grade 2) and severe (Grade 3), based on an international questionnaire. The physical exam was guided by the ankle-brachial index (ABI), with values below 0.9 indicating PAD. Data analysis involved Pearson s chi-squared test, Fisher s exact test and the Kruskal-Wallis test for the comparison of ABI values based on combined SAH-ED, using the Bonferroni correction. Dependence analysis was employed to determine the following associations: ED x ABI, ED x SAH, SAH x ABI and SAH x ABI x ED. Logistic regression analysis was performed to relate the degree of ED with the combination of SAH and ABI, considering a 5% alpha error. Results: Among the 125 patients studied, 22 (17.6%) had mild ED, 50 (40.0%) had moderate ED and 53 (42.4%) had severe ED. Regarding the ABI, 40 (32.0%) patients had values equal to or greater than 0.9, whereas 85 (68.0%) have values lower than 0.9, indicting the occurrence of PAD. The comparison between the median ABI of patients with different degrees of ED demonstrated significant differences between Grades 1 and 3 (p = 0.0009) as well as between Grades 2 and 3 (p = 0.0131). The dependence diagram revealed the following: 1) Grade 3 ED was associated with PAD in the comparison between patients with ABI < 0.9 and those with ABI &#8805; 0.9 (p = 0.013); 2) Grade 3 ED was associated with SHT in the comparison between normotensive and hypertensive patients (p = 0.002); 3) Grade 3 ED was associated with SAH + PAD in the comparison between normotensive and hypertensive patients with ABI < 0.9 and normotensive and hypertensive patients with ABI &#8805; 0.9 (p = 0.002). In patients with PAD, hypertensive patients exhibited Grade 3 ED more than normotensive patients (p = 0.015). The logistic regression of the association between ED and the SAH-ABI combination with the reference N-ABI &#8805; 0.9 demonstrated a tendency (p < 0.0005) toward an increased risk of a greater degree of ED obeying the following order: SAH-ABI &#8805; 0.9, SAH-ABI < 0.9 and N-ABI < 0.9. Conclusions: The impairment of the ED grade corresponds to a decrease of ABI, suggesting evolution of PAD in these patients. There was a significant association among Grade 3 ED x PAD, Grade 3 ED x SAH, and SAH x PAD. Hypertensive patients exhibited Grade 3 ED significantly more than normotensive patients. Systemic arterial hypertension may have a compensatory effect against erectile dysfunction in patients with peripheral arterial disease. / Introdução: A avaliação da disfunção erétil (DE) como sintoma precoce de disfunção endotelial e aterosclerose pode ser relevante na identificação de pacientes com elevado risco cardiovascular. Objetivo: Estudar a influência da hipertensão arterial sistêmica (HAS) e doença arterial periférica (DAP) em pacientes com disfunção erétil. Casuística e Método: Foram estudados 125 pacientes com DE, cuja idade variou de 19 a 88 anos (59,82 ± 10,48 anos), independente de raça, provenientes da região de São José do Rio Preto, SP, no período de março a outubro/2011. A DE foi classificada em leve (grau 1), moderada (grau 2) e grave (grau 3) utilizando questionário internacional de função erétil. Foi realizado exame físico direcionado por meio do índice tornozelo-braquial (ITB), sendo que valores abaixo de 0,9 indicam DAP. A análise de dados foi efetuada por meio dos testes qui-quadrado de Pearson, exato de Fisher, Kruskal-Wallis para comparação de ITB segundo combinação HAS-DE utilizando-se correção de Bonferroni. Análise de dependência foi utilizada para determinar associação entre DE x ITB, DE x HAS, HAS x ITB e HAS x ITB x DE. Regressão logística foi usada para relacionar grau de DE com a combinação HAS e ITB, considerando erro alfa de 5%. Resultados: Dos 125 pacientes estudados, 22 (17,6%) tinham DE leve, 50 (40,0%) moderada e 53 (42,4%) grave. Com relação ao ITB, 40 (32,0%) pacientes apresentaram valores iguais ou acima de 0,9 e 85 (68,0%) valores inferiores a 0,9, indicando a ocorrência de DAP. O resultado da comparação entre mediana do ITB de pacientes com diferentes graus de DE mostrou diferenças significativas entre os graus 1 e 3 (p = 0,0009) e 2 e 3 (p = 0,0131). Pelo diagrama de dependência para comparação dos graus de DE: 1- entre ITB < 0,9 com ITB &#8805; 0,9, constatou-se que o grau 3 está associado à DAP (p= 0,013); 2- entre normotensos com hipertensos, constatou-se que o grau 3 está associado a HAS (p= 0,002); 3- entre portadores de ITB < 0,9 normotensos e hipertensos com aqueles com ITB &#8805; 0,9 normotensos e hipertensos, constatou-se que o grau 3 está associado a HAS e DAP (p= 0,002). Considerando pacientes portadores de DAP com e sem HAS, hipertensos apresentaram mais DE grau 3 quando comparados com normotensos (p = 0,015). A regressão logística do grau de DE sobre a combinação HAS-ITB, com referência em N-ITB &#8805; 0,9, demonstrou tendência (p<0,0005) a crescimento de risco de aumento de grau de DE segundo a ordem: HAS-ITB &#8805; 0,9, HAS-ITB < 0,9, N-ITB < 0,9. Conclusões: A piora do grau de DE corresponde à redução do ITB, sugerindo evolução da DAP nesses pacientes. Houve associação significativa entre DE grau 3 e DAP; DE grau 3 e HAS, e HAS e DAP. Pacientes hipertensos apresentaram estatisticamente mais DE grau 3 em relação a normotensos. A HAS pode ter efeito compensatório contra a DE em pacientes com DAP.

Peripheral vascular diseases such as peripheral artery disease (PAD) and critical limb ischemia (CLI) are growing at an ever-increasing rate in the Western world due to an aging population and the incidence of type II diabetes. A growing economic burden continues because these diseases are common indicators of future heart attack or stroke. Common therapies are generally limited to pharmacologic agents or endovascular therapies which have had mixed results still ending in necrosis or limb loss. Therapeutic angiogenic strategies have become welcome options for patients suffering from PAD due to the restoration of blood flow in the extremities. Capillary sprouting and a return to normoxic tissue states are also demonstrated by the use of angiogenic cytokines in conjunction with bone marrow cell populations. To this point, it has been determined that spatial and temporal controlled release of growth factors from vehicles provides a greater therapeutic and angiogenic effect than growth factors delivered intramuscularly, intravenously, or intraarterialy due to rapid metabolization of the cytokine, and non-targeted release. Furthermore, bone marrow cells have been implicated to enhance angiogenesis in numerous ischemic diseases due to their ability to secrete angiogenic cytokines and their numerous cell fractions present which are implicated to promote mature vessel formation. Use of angiogenic peptides, in conjunction with bone marrow cells, has been hypothesized in EPC mobilization from the periphery and marrow tissues to facilitate neovessel formation. For this purpose, controlled release of angiogenic peptides basic fibroblast growth factor (FGF-2) and granulocyte-colony stimulating factor (G-CSF) was performed using tunable ionic gelatin hydrogels or fibrin scaffolds with ionic albumin microspheres. The proliferation of endothelial cell culture was determined to have an enhanced effect based on altering concentrations of growth factors and method of release: co-delivery versus sequential. Scaffolds with these angiogenic peptides were implanted in young balb/c mice that underwent unilateral hindlimb ischemia by ligation and excision of the femoral artery. Endpoints for hindlimb reperfusion and angiogenesis were determined by Laser Doppler Perfusion Imaging and immunohistochemical staining for capillaries (CD-31) and smooth muscle cells (alpha-SMA). In addition to controlled release of angiogenic peptides, further studies combined the use of a fibrin co-delivery scaffold with FGF-2 and G-CSF with bone marrow stem cell transplantation to enhance vessel formation following CLI. Endpoints also included lipophilic vascular painting to evaluate the extent of angiogenesis and arteriogenesis in an ischemic hindlimb. Tissue engineering strategies utilizing bone marrow cells and angiogenic peptides demonstrate improved hindlimb blood flow compared to BM cells or cytokines alone, as well as enhanced angiogenesis based on immunohistochemical staining and vessel densities.

Le vieillissement de la population mondiale s’accompagne de l’augmentation de la prévalence des maladies non transmissibles, dont certaines liées à l’athérosclérose. Les études épidémiologiques sur l’artériopathie oblitérante des membres inférieurs (AOMI) ont été majoritairement menées dans les pays occidentaux. Peu d’entre elles sont conduites dans les pays à faible et moyen revenu, comme les pays africains alors que la rapide transition socio-économique de ces pays entraîne une modification épidémiologique importante. Le programme EPIDEMCA (Épidémiologie des Démences en Afrique Centrale), enquête épidémiologique transversale multicentrique en population générale âgée de 65 ans et plus, a été mené en zones rurales et urbaines de deux pays d’Afrique Centrale: la République Centrafricaine (RCA) et la République du Congo (RDC), entre 2011 et 2012. Durant la première phase, l’enquête épidémiologique a permis de déterminer la prévalence de l’AOMI et d’analyser les facteurs de risque associés. L’AOMI a été définie par un Index de Pression Systolique (IPS) ≤ 0,9. Parmi les 1871 participants évalués sur le plan vasculaire, la prévalence de l’AOMI a été de 14,8% et atteignant 22,2% pour les sujets âgés de 80 ans et plus. Une prévalence plus importante de l’AOMI a été retrouvée dans les zones urbaines en RDC (20,7% versus 14,4% dans la zone rurale, p=0,0114). Cette différence n’a pas été retrouvée en RCA (11,5% urbain versus 12,9%, rural p=NS). Après ajustement à tous les possible facteurs confondants, des facteurs de risque associés avec l’AOMI ont été décrits : l’âge (OR: 1,03 ; p=0,0039), l’hypercholestérolémie (OR: 1,88 ; p=0,0034), le tabac (OR: 1,78 ; p=0,0026). Plus particulièrement, cette première étude en population générale ayant analysé spécifiquement le rôle de la dénutrition (Index de Masse Corporelle <18) dans l’AOMI met en évidence une association significative (OR: 2,09; p=0,0009) et ceci autant chez les hommes que chez les femmes (OR: 2,82; p= 0,0038 et respectivement OR: 1,75; p= 0,0492). Lors de la deuxième phase de l’étude, ayant permis la confirmation de l’atteinte cognitive, nous avons analysé l’association entre l’IPS et la présence des troubles cognitifs. La prévalence des troubles cognitifs s’est avérée être de 13,6%, plus importante chez les sujets avec IPS≤0,9 et IPS≥1,4 que chez les sujets avec 0,9<IPS<1,4 (20,1% et 17% versus 12%, p=0,0024). La présence des troubles cognitifs a été significativement associée avec l’âge (OR: 1,09; p<0,0001), le sexe féminin (OR: 2,36; p<0,0001), la consommation de tabac (OR: 1,78; p=0,0026) et l’IPS <0,90 (OR: 1,52; p=0,0359). Ce travail, s’inscrivant dans le cadre du programme EPIDEMCA, contribue à une meilleure connaissance de l’épidémiologie de l’AOMI sur le continent Africain. Il souligne la haute prévalence de cette pathologie, comparable aux pays occidentaux décrit les facteurs de risque spécifiques associés et met en évidence l’importance des outils de diagnostic de l’athérosclérose (IPS), fiables, peu coûteux et d’utilisation facile dans le dépistage des sujets à risque polyvasculaire. / With the aging of the global population, the prevalence of non-communicable, including cardiovascular, diseases is increasing. While epidemiological studies on peripheral artery disease (PAD) have been mainly conducted in high-income countries, a few have been carried out in low-and middle-income countries, including in Africa. EPIDEMCA (Epidemiology of Dementia in Central Africa) is a cross-sectional population-based study in rural and urban areas of two countries of Central Africa: Central African Republic (CAR) and the Republic of Congo (ROC). Overall, its aim was to investigate the health status in aging population in Central Africa, with a special focus on cognitive disorders, PAD (Ankle-Brachial Index (ABI) ≤0.90). and cardiovascular risk factors as well as their inter-relationship. The EPIDEMCA program was carried out, among people aged 65 years and over, between 2011 and 2012. Among 2002 subjects who agreed to participate, reliable demographic and vascular data were available in 1871 subjects.Overall, the prevalence of PAD was 14.8% reachting 22.2% after the age of 80. The prevalence was higher in ROC than in CAR (17.4% vs. 12.2%, p=0.0071) and in females than males (16.6% vs. 11.9%, p=0.0122). Higher rates of PAD were found in urban area in ROC (20.7% vs. 14.4% in rural area, p=0.0114), not in CAR (11.5% vs. 12.9%, p=ns). In the multivariate analysis, PAD significantly associated factors were described: age (OR: 1.03; p=0.0039), dyslipidemia (OR: 1.88; p=0.0034), smoking (OR: 1.78; p=0.0026), and more specifically undernutrition (OR: 2.09, p=0.0009). Undernutrition was still significantly associated with PAD after adjustment to all potential confounding factors in males as well as in females (OR: 2.82, p= 0.0038 respectively OR: 1.75, p= 0.0492). As epidemiological research on the implication of atherosclerosis in the development of cognitive impairment in general population is lacking in Africa, we focused on the role of ABI as an available marker of atherosclerosis, providing independent and incremental information on subjects’ susceptibility to present cognitive disorders.The prevalence of cognitive impairment among the study participants was 13.6%, higher in subjects with ABI≤0.9 and ABI≥1.4 than those with 0.9<ABI<1.4 (20.1% and 17% vs. 12%, p=0.0024). Cognitive impairment was significantly associated with age (OR: 1.09; p<0.0001), female gender (OR: 2.36; p<0.0001), smoking (OR: 1.78; p=0.0026) and low (≤0.90) ABI (OR: 1.52; p=0.0359). The EPIDEMCA program contributes to a better understanding of PAD in general African population. It highlights the the high prevalence of PAD on the African continent, describes specifically associated risk factors and underlines the importance of an available, inexpensive marker of atherosclerosis in order to detect risk populations in these countries.