Philosophiae Doctor - PhD / Background: There is compelling body of evidence that coronary heart disease (CHD) risk factors are present in people of all ages. The extent to which the problem exists in university students in South Africa (SA) has not been confirmed in the literature. Furthermore, the effects of physical activity, physical fitness, diet and health behaviours on CHD risk factors has not been studied extensively in SA and needs further investigation. Aim: The aim of the study was to assess the impact of multiple behaviour health intervention strategies on CHD risk, health-related physical fitness(HRPF) and healthrisk behaviours (HRB) in first year students at the University of the Western Cape (UWC). It was hypothesized that exposure to various health behavioural interventions would reduce CHD risk factors in subjects at moderate risk, and improve health-related physical fitness, as well as health-risk behaviours.Methods and Study Design: An experimental study design was used wherein subjects at moderate risk for CHD were identified and exposed to multiple health behavioural interventions for 16 weeks in order to determine the impact of the various interventions on CHD risk, health-related physical fitness and health-risk behaviours. Population and Sample: The target population consisted of first year students at UWC aged 18 – 44 years who were screened and a sample of 173 subjects were identified as being at moderate risk for CHD. Next, the subjects were randomly assigned to a control and four treatment groups, namely, health information, diet, exercise, and a multiple group that included all three treatments. The intervention, based upon Prochaska‟s Transtheoretical Model of behaviour change, continued for a period of 16 weeks and, thereafter, the subjects were retested. Data Collection Process: Subject information was obtained using self-reported questionnaires, namely, the physical activity readiness questionnaire (PAR-Q), the stages of readiness to change questionnaire (SRCQ), the international physical activity questionnaire (IPAQ), and the healthy lifestyle questionnaire (HLQ), together with physical and hematological (blood) measurements. The measurements taken before and after the intervention programme were the following:• Coronary heart disease risk factors, namely: family history, cigarette smoking, hypertension, obesity, dyslipidemia, impaired fasting glucose and a sedentary lifestyle; • Health-related physical fitness, namely: body composition, cardiovascular fitness, muscular strength, muscular endurance, and flexibility; and • Health-risk behaviours, namely: physical activity, nutrition, managing stress, avoiding destructive habits, practising safe sex, adopting safety habits, knowing firstaid, personal health habits, using medical advice, being an informed consumer, protecting the environment and mental well-being. Types of interventions: A control group was used in which subjects did not receive any treatment. The health behavioural interventions were arranged into four groups of subjects that received either the health information, diet, exercise or a combination of all three individual treatments. Statistical analyses of data: In the analyses of the data, the procedure followed was that where the outcome variable was approximately normally distributed, the groups were compared using a two-sample t-test. For outcomes with a highly non-normal distribution or ordinal level data, the nonparametric Wilcoxon Rank Sum test was used for group comparisons. To account for baseline differences, repeated measures analysis of variance was used. In the case where nonparametric methods were appropriate, analysis was done using Cochran-Mantel-Haenszel (CMH) methodology stratifying on the baseline values. For the case of nominal level outcomes, groups were compared by Chi-square tests for homogeneity of proportions. When baseline values needed to be incorporated into the analysis, this was done using CMH methodology. Main Outcome Measures: The main outcome measures tested in the study related to the three areas of investigation, namely: • Modifiable CHD risk factors: systolic and diastolic blood pressure, cigarette smoking, total cholesterol (TC) concentration, high-density lipoprotein (HDL) cholesterol concentration, low-density lipoprotein (LDL) cholesterol concentration, triglycerides, fasting glucose, body mass index, waist circumference, waist-hip ratio and physical inactivity; • Health-related physical fitness: body mass, percent body fat, absolute body fat, percent lean body mass, absolute lean body mass, the multi-stage shuttle run, handgrip strength, repeated sit-ups in a minute, and the sit-and-reach test; and • Health-risk behaviours: physical activity, nutrition, managing stress, avoiding destructive habits, practising safe sex, adopting safety habits, knowing first aid, personal health habits, using medical advice, being an informed consumer, protecting the environment and mental well-being. Results: The results showed significant decreases for body mass, waist and hip circumferences, resting heart rate, systolic blood pressure, cigarette smoking and a sedentary lifestyle (p < .05) primarily in the multiple group. No significant differences were recorded for blood biochemistry, however, favourable trends were observed in the lipoprotein ratios. For health-related physical fitness, only the multiple group showed significant (p < .005) improvements in predicted maximal oxygen consumption ( O2max), body composition, muscular strength and muscular endurance. The exercise group also recorded significant differences in muscular endurance. In all groups, including the controls, no significant differences were found for stature, waist-hip ratio, and flexibility at pre- and post-test. Overall, the participants reflected positive health behaviours, especially for managing stress, avoiding destructive habits, practising safe sex, adopting safety habits, personal health habits and mental well-being at pre- and post-test. The intervention programme had a corrective influence on providing the participants with a more realistic perception of their level of physical activity and nutritional habits. The participants scored poorly on being informed consumers and for recycling waste both at pre- and post-test. A substantial net reduction in CHD risk factors as well as in cumulative risk was achieved with treatment that impacted positively on the re-stratification of participants at moderate risk. In terms of treatment efficacy, the dietary intervention appeared to be the least effective (10.91%), with health information and exercise sharing similar levels of efficacy (32.81% and 33.93%, respectively) and, the combined treatment in the multiple group stood out as the most effective treatment (50.00%), and supported the hypothesis of the study. Conclusions: The net and cumulative decline in CHD risk factors was substantial with treatment and was directly related to the number of treatments administered. The evidence suggests that such multiple health behaviour interventions when implemented through a university-based setting have substantial benefits on reducing CHD risk and may be of considerable public health benefit. Key messages • Despite being a relatively educated population, a substantial number of first year university students are at considerable heart disease risk. • Physical inactivity constitutes one of the main CHD risk factors amongst first year students and, together with smoking, place many of them at moderate CHD risk. • The effectiveness of health behavioural strategies designed to modify lifestyle and prevent coronary heart disease is supported by this study.

Introduction: Atherosclerosis remains asymptomatic until it progresses to cause flow-limiting disease. Identifying patients at high risk in the early stages of the atherosclerotic process may allow modification of cardiovascular risk by effective preventive strategies. Various non-invasive tests have been studied and have shown promising results in predicting future adverse cardiovascular events. The objective of this study was to establish the carotid ultrasonographic markers that best correlate with angiographic coronary artery disease (CAD) and the relationship between left ventricular geometry, carotid atherosclerosis, biomarkers and CAD in patients with unobstructed coronary arteries, chronic stable angina (CSA) and acute coronary syndromes (ACS). Methods: Carotid ultrasound examination, echocardiography and serum biomarker estimation were performed in consecutive patients who underwent coronary angiography for evaluation of stable or acute chest pain. Results: A total of 146 subjects were recruited into the study with a mean age of 56.9 ± 10.6 (range 29 to 85) years; 120 were men (82%) and 26 (18%) women. Twenty-one percent of the study population had unobstruced coronaries, 42% had stable CAD and 37% had presented with ACS. There was no significant difference in the carotid intima media thickness (CIMT) measurements between the three groups. CIMT correlated with abnormal left ventricular geometry but not with the presence or severity of CAD. The presence of carotid plaque and plaque score correlated with obstructive CAD, but was not significantly different between stable CAD and ACS patients. There was a trend towards more echogenic plaque in the stable CAD group. The composite score of IMT and plaque was positively correlated with the presence and severity of CAD. The averaged myocardial peak systolic and early diastolic velocities were significantly lower in those with obstructive CAD. CRP and osteopontin levels were higher in the ACS patients. Conclusions: Carotid plaque and not CIMT was associated with angiographic coronary artery disease. Averaged systolic and early diastolic myocardial velocities by tissue doppler imaging correlated with obstructive CAD. Novel serum biomarkers are promising and further studies are needed.

First degree relatives (FDRs) of subjects with early onset of coronary heart disease (CHD) have higher risk of developing cardiovascular disease. We verified early CHD by angiography in the index patients and extensively phenotyped their FDRs to investigate the relationship of traditional and non-traditional cardiovascular risk factors to carotid ultrasound and coronary calcium scoring findings. B-mode carotid ultrasound was used to assess the combined intima-media thickness and plaque burden in 111 FDRs. The biochemical and anthropometrical characteristics of the FDRs were compared with those of healthy controls matched for sex, age, ethnicity and BMI. Odds ratios indicate that FDRs are more likely to have positive carotid ultrasound findings compared to controls; 2.23 (95% CI 1.14 – 4.37) for intima-media thickness and 2.3 (95% CI 1.22 - 4.35) for average total thickness. In multivariate analysis positive carotid ultrasound findings were higher in FDRs independent of age, gender, total cholesterol over HDL-c ratio, systolic blood pressure and smoking but not homocysteine which had higher values in FDRs compared to controls. In conclusion FDRs of patients with angiographically confirmed CHD have higher burden of subclinical atherosclerosis even when considered in the context of traditional risk factors. Coronary artery calcium scoring (CAC), assessed by 64-slice multi-detector computed tomography (MDCT), was used to assess burden of subclinical atherosclerosis in 57 FDRs compared to controls. FDRs have a two-fold increase in risk of having CAC positive findings; odds ratios for the 75th percentile was 1.96 (95%CI 1.04 – 3.67, p<0.05) while for the 90th percentile odds ratio was 2.59 (95% 1.232 – 5.473, p<0.05). In summary, the risk of significant CAC findings, measured by 64-slice MDCT, is two-fold higher in FDRs than controls. These findings correlate highly with carotid ultrasound findings in the same cohort. Different thresholds for CAC may be appropriate when assessing male versus female FDRs. Together increased carotid ultrasound findings and CAC scoring results in FDRs of patients with validated early onset of CHD suggest these imaging techniques as potentially useful tools in cardiovascular risk assessment that will go above and beyond the current diagnostic algorithms. / Medicine, Faculty of / Pathology and Laboratory Medicine, Department of / Graduate

Angiogenic cell therapy is currently being developed as a treatment for coronary artery disease (CAD); however, endothelial dysfunction (ED), commonly found in patients with CAD, impairs the ability for revascularization to occur. We hypothesized that culture on a collagen matrix will improve survival and function of circulating progenitor cells (CPCs) isolated from a mouse model of ED. Overall, ED decreased the expression of endothelial markers in CPCs and impaired their function, compared to normal mice. Culture of CPCs from ED mice on collagen was able to increase cell marker expression, and improve migration and adhesion potential, compared to CPCs on fibronectin. Nitric oxide production was reduced for CPCs on collagen for the ED group; however, CPCs on collagen had better viability under conditions of serum deprivation and hypoxia, compared to fibronectin. This study suggests that a collagen matrix may improve the function of therapeutic CPCs that have been exposed to ED.

Background-Pulmonary artery hypertension (PAH) is characterized by progressive vascular changes causing increased pulmonary resistance and eventual right heart failure (HF). It has been suggested that altered myocardial substrate utilization may be associated with right HF, however these changes have not yet been well characterized. The aim of this study was to evaluate in vivo right ventricular (RV) function and RV glucose and fatty acid metabolism in an experimental model of PAH using non-invasive positron emission tomography (PET) imaging and to investigate the effect of a novel endothelin receptor antagonist, Macitentan, on the development of PAH and RV energetics. Methods and Results-Severe PAH was induced in a total of 11 male Sprague-Dawley rats using a single injection of Sugen5416 followed by chronic hypoxia. The rats were then randomized to treatment or no treatment with Macitentan (30 mg/kg daily) Five and eight weeks post injection, substrate utilization was serially assessed with 2-[18F]fluoro-2-deoxyglucose (FDG) and 4-[18F]fluoro-6-thia-heptadecanoate (FTHA) PET scans for glucose and fatty acid metabolism respectively, and reported as a standardized uptake value (SUV). This data was correlated with in vivo functional measurements with echocardiography and multi gated acquisition scans. The Sugen-hypoxia (SuHx) model resulted in an increase in RV FDG uptake over 8 weeks (SUV control: 1.56 ± 0.38, week 5 SuHx: 4.06 ± 1.90, week 8 SuHx: 4.00 ± 1.60, p<0.005 between control and week 5 SuHx). RV FTHA data showed a trend towards increased uptake with onset of PAH at week 5 SuHx (SUV control: 1.50 ± 0.40, week 5 SuHx: 3.06 ± 1.10, p>0.05). Macitentan significantly decreased RV FDG uptake (SUV week 8 SuHx: 4.00 ± 1.60, week 8 SuHx +ERA: 2.54 ± 0.90, p<0.05). This was associated with improved RV ejection fraction (PAH week 8 untreated: 53.15 ± 9.9% vs PAH week 8 treated: 73.22 ± 4.8%, p<0.01) and improved pulmonary artery pressures measured by pulmonary artery acceleration time (PAH week 8 untreated: 17.32 ± 2.30 ms vs. PAH week 8 treated: 24.38 ± 3.90 ms, p<0.001). There was a strong correlation between increased pulmonary artery pressures and increased RV FDG uptake (r=0.87, p=0.001) as well as a significant inverse relationship between improved RV ejection fraction and decreased RV FDG uptake (r=-0.72, p=0.01). Conclusion-PAH is associated with metabolic changes in the RV, characterized by increased glucose uptake and a trend towards increased RV fatty acid uptake with onset of PAH. Macitentan attenuated RV FDG uptake and significantly increased RV function as well as hemodynamics compared to untreated group.

Increasingly, cell-based therapy with autologous progenitor populations, such as endothelial progenitor cells (EPC), are being utilized for treatment of vascular diseases. However, both the number and functional capacity are diminished when cells are derived from patients with established risk factors for coronary artery disease (CAD). Herein, we report that inhibition of glycogen synthase kinase 3 (GSK) can improve both the number and function of endothelial progenitor cells in patients with CAD or diabetes mellitus (DM) leading to greater therapeutic benefit. Specifically, use of various small molecule inhibitors of GSK (GSKi) results in a 4-fold increased number of EPCs. Moreover, GSKi treatment improves the functional profile of EPCs through reductions in apoptosis, improvements in cell adhesion through up-regulation of very-late antigen-4 (VLA-4), and by increasing paracrine efficacy by increasing vascular endothelial growth factor (VEGF)secretion. Therapeutic improvement was confirmed in vivo by increased reendothelialization(RE) and reductions of neointima (NI) formation achieved when GSKi-treated cells were administered following vascular injury to CD-1 nude mice. Because cell-based therapy is technically challenging, we also tested a strategy of local delivery of GSKi at the site of arterial injury through GSKi-eluting stents. In vitro, GSKi elution increased EPC attachment to stent struts. In vivo, GSKi-eluting stents deployed in rabbit carotid arteries resulted in systemic mobilization of EPCs, improved local RE, and important reductions in in-stent NI formation. Finally, we tested the ability of GSKi to improve EPC-mediated arterial repair in patients with DM. As in patients with CAD, GSKi treatment improved EPC yield and diminished in vitro apoptosis. Utilizing a proteomics approach, we identified Cathepsin B (catB) as a differentially regulated protein necessary for reductions in apoptosis. Indeed, antagonism of catB prevented GSKi improvements in GSKi treated EPC mediated arterial repair in a xenotransplant wire injury model. Thus, our data demonstrates that GSKi treatment results in improvements in EPC number and function in vitro and in vivo resulting in enhanced arterial repair following mechanical injury. Accordingly, GSK antagonism is an effective cell enhancement strategy for autologous cell-based therapy with EPCs from high risk patients such as CAD or DM.

Atherosclerotic renovascular disease (ARVD) is a significant cause of chronic kidney disease (CKD) and is associated with an increased risk for cardiovascular morbidity and mortality. Randomised controlled trials, representing over 2100 patients, have failed to demonstrate any prognostic benefit of percutaneous renal revascularisation when utilised in addition to standard medical therapy. This negative finding has been interpreted in three ways. Firstly, that ARVD may be an association of CKD and not a specific disease process. Secondly, that published studies have recruited low-risk patients who are least likely to benefit from revascularisation. Thirdly, that the focus of treatment for patients with ARVD should be optimal medical therapy, not renal revascularisation. This research project had a series of linked aims. These were investigated in two large patient cohorts that had been accumulated at this centre over the last decade. These cohorts comprised > 900 patients with ARVD, the Salford Renovascular Database (SRVD), and > 2500 patients with all-cause CKD, the Chronic Renal Insufficiency Standards Implementation Study (CRISIS). The first aim was to consider whether ARVD should be considered as a specific cause of CKD. Here risks for death and progression to renal replacement therapy were compared between patients having ARVD as their primary cause of renal failure and patients with other coded causes of CKD. In this analysis, patients with ARVD had a greater risk for death and a lesser risk for RRT than patients with other forms of CKD.The second aim of this thesis was to consider if specific patient sub-groups of ARVD could be identified. Patients in the SRVD with currently accepted high- risk clinical presentations were selected and outcomes compared to patients without a high-risk presentation. In this analysis, presentation with flash pulmonary oedema (but with not refractory hypertension or rapidly declining renal function) was associated with an increased risk for death and cardiovascular event. When the effects of revascularisation were considered in patients with high-risk presentations, a mortality benefit was observed in patients with flash pulmonary oedema and in patients presenting with rapidly declining renal function and refractory hypertension in combination. A separate analysis was performed in the SRVD to consider if a high-risk sub-group of ARVD patients could be identified using laboratory measurements. Here, a classification tree methodology was employed to identify ARVD patients with the greatest risk for progression to end stage kidney disease. The results of this analysis were converted into a practically applicable clinical scoring system incorporating renal function, proteinuria, medications, smoking history and renal artery occlusion. The final aim of this thesis was to describe how the majority of ARVD patients should be treated. In this analysis of the SRVD effects of treatment with anti- platelet and beta-blocker therapy were considered, and shown to be associated with reduced risks for cardiovascular events and death.

The initial hours following an ischaemic event in the brain represent a critically important window in which therapeutic interventions to reduce neuronal damage and improve patient outcome can be made. Nevertheless, the dynamics of cerebral blood flow and oxygenation, as well as the local physiological changes, in the first few hours after reperfusion following ischaemic stroke are not well understood. In the first study, a remote filament approach was used to obtain multispectral imaging data before, during and after middle cerebral artery occlusion to investigate early changes in haemodynamic concentration of oxy-/deoxy-haemoglobin and total blood volume, in anaesthetised mice. We use immunohistochemistry to establish the extent of cortical injury and correlate the severity of damage with the change of oxygen perfusion during and after the ischaemic event. Increased numbers of platelets and activated microglia, expression of interleukin-1α, evidence of BBB breakdown and neuronal stress are all seen within the stroked hemisphere of MCAo mice and correlate with the severity of oxy-haemoglobin concentration deficit at experimental but not with the change in oxy-haemoglobin concentration during the acute stroke. In the second study, we used the same remote filament and optical imaging approach to investigate the effects of acute systemic inflammation on haemodynamics pre, during, and after induced cerebral ischaemia. We found that an acute systemic inflammatory challenge exacerbates oxy-haemoglobin deficit after 3 h of reperfusion following an ischaemic event. We investigated known pathophysiological markers to elucidate potential mechanisms that may contribute to this exacerbated oxygenation deficit and found hyper-coagulated platelets within the large and microvessels of the ipsilateral cortex. Our findings demonstrate that despite initial restoration of HbO2 supply after 30 min MCAo there is a delayed compromise that coincides with inflammatory processes that could be a future target for improved stroke outcome after thrombolysis. We also show that acute systemic inflammation exacerbates this oxy-haemoglobin deficit after an ischaemic challenge and increases pathophysiology.

Orientador: Andrei Carvalho Sposito / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-24T12:32:38Z (GMT). No. of bitstreams: 1 Bellinazzi_VeraRegina_D.pdf: 1427871 bytes, checksum: 13c49eabda6b5a189f64c4a1db75108b (MD5) Previous issue date: 2014 / Resumo: O ultrassom da artéria carótida tem sido proposto como uma maneira de melhorar a predição de eventos cardiovasculares (CV). Apesar da espessura íntima-média (EIM) carotídea ter sido extensivamente associada a eventos CV, o acréscimo desta medida a algoritmos de predição de risco resultou em pouco ou nenhum ganho adicional à predição de risco. A proposta deste estudo foi comparar a performance da EIM, diâmetro sistólico (DS), velocidade de fluxo sistólico (VFS) e a razão VFS/DS carotídeos como preditores de eventos CV maiores em uma amostra de indivíduos hipertensos. Uma coorte de 403 pacientes hipertensos (idade media 59.2?12.4 anos; 42% homens) foi acompanhada por uma mediana de 1260 (714) dias, e 27 indivíduos sofreram eventos CV maiores. No início do seguimento, os participantes realizaram avaliação clínica, laboratorial, ecocardiográfica e ultrassonográfica de carótida. Os indivíduos com baixa (mediana) DS apresentaram um pior desfecho clinico quando comparados com aqueles com baixa VFS ou alto DS isoladamente, o que sugere um efeito aditivo destas duas variáveis. A curva atuarial do tempo para o evento CV maior demonstrou pior desfecho para indivíduos com baixo índice VFS/DS comparado com aqueles com alto VFS/DS (p<0.001). Na análise de regressão de Cox ajustada para EIM carotídea e alto-risco CV definido clinicamente, baixo índice VFS/DS manteve-se significativamente associado a eventos CV maiores (Exp(B)[95%CI]=3.69[1.37-9.96]; p=0.01). Além disso, as áreas sobre a curva ROC foram para alto risco CV (0.612; p=0.051), alta EIM (0.601; p=0.009) e baixo índice VFS/DS (0.669; p=0.003) usando eventos CV maiores como desfecho binário. Enfim, concluímos que baixo índice VFS/DS está associado a pior desfecho CV em pacientes hipertensos independente de modelos de predição de risco CV e da EIM carotídea / Abstract: Carotid artery ultrasound examination has been proposed as a way to improve cardiovascular (CV) events prediction. Although carotid intima-media thickness (IMT) has been extensively associated with CV events, modest or even no improvements in prediction were gained by adding this parameter to prediction models. The aim of this study was to compare the performance of common carotid IMT, diameter (AD), flow velocity (FV) and FV/AD ratio as predictors of major CV events (MACE) in a sample of hypertensive subjects. A cohort of 403 hypertensive patients (mean age, 59.2?12.4 years; 42% men) was followed-up for a median of 1260(714) days, and 27 subjects suffered MACE. At baseline, participants were evaluated by clinical, laboratory, echocardiographic and carotid ultrasound analysis. Patients with low (median) AD presented the worse clinical outcome as compared with those with isolated low FV or high AD suggesting an additive effect of these two variables. Actuarial analysis of time to MACE demonstrated worse outcome for individuals with low FV/AD ratio compared to those with high FV/AD ratio (p<0.001). In Cox-regression analyses adjusted for carotid IMT and clinically-defined high CV risk, low FV/AD ratio remained significantly associated with MACE (Exp(B)[95%CI]=3.69[1.37-9.96]; p=0.01). Furthermore, the areas under the receiver-operating curves (C-statistics) were for clinically defined high-risk (0.612; p=0.051), high IMT (0.601; p=0.009) and low FV/AD ratio (0.669; p=0.003) using MACE as a binary outcome. In conclusion, low FV/AD ratio is associated with a poor outcome in hypertensive patients independent of CV prediction models and carotid IMT / Doutorado / Clinica Medica / Doutora em Clínica Médica

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