Patients with Peripheral Arterial Disease have a reduced capacity for exercise, the exact causes of which are poorly understood. This thesis investigated alternative testing procedures that aim to provide a more complete and precise description of the exercise capacities of these patients. Furthermore, the potential roles of gastrocnemius muscle fibre morphometry, capillary supply and glycogen stores in the exercise tolerance of PAD patients were studied. Study one aimed to determine the effect of test repetition on maximal exercise performance and test-to-test variability in PAD patients using an incremental treadmill walking test (T) (n=5), an incremental cycle test (C) (n=5), and incremental endurance (PF-endurance) and maximal strength (PF-strength) plantar flexion tests (n=5). Tests were conducted once per week for eight weeks. Performance was stable on the T (~530 s) and C (~500 s) tests across the eight weeks. Test-to-test variance on T decreased from 16%CV (CV: coefficient of variation) to 6%CV (p=.21,NS), and from ~8%CV to 2%CV on C (p<.05) over the eight week period. Variance of peak gas exchange variables tended to decrease with performance variance on both tests; however, other physiological variables, and the associated variance levels, were stable throughout the study. PF strength (635-712N) gradually increased over the initial 2-3 weeks (p<.05) which was accompanied by a reduction in variance from ~8%CV to ~3%CV (p<.05). Similarly, PF endurance increased over the first two weeks (~32,000 to 41500 N.s-1) while variance of this measure fell from ~21%CV to ~10%CV (p<.05) over the study duration. It is concluded that the implementation of familiarisation sessions leads to a reduction in whole body and local calf muscular performance variance in patients with PAD. Using a randomised crossover design, study two aimed to compare performance and the physiological and symptomatic responses between a T test and a C test in 16 patients with PAD. Peak exercise time on C (690 s) was greater than that on T (495 s); however the two were significantly correlated (n=16, r=.69, p<.05). Peak HR (120 bpm), VO2 (~1.22 l.min-1) and rate pressure product (~20') did not differ between the two tests, nor did the post exercise ankle pressure (T: 56; C: 61 mmHg). In two subjects with lower back pain during C, the ankle pressure of their "worst" limbs failed to fall by >10mmHg. Performance on both the T and C tests was closely related to the onset of leg symptoms; however the site of pain during C was much more variable than during T. Incremental cycle testing would overcome some of the limitations of treadmill testing (e.g. measurement of mechanical work), and it appears to be an acceptable alternative for measuring the exercise capacity and physiological exercise responses in known claudicants. Use of cycle ergometry for the diagnosis of PAD requires testing in the general population. Study three aimed to compare whole body (T test and C test) and local calf muscular (PF strength and endurance) exercise performance between 16 PAD patients (age: 63 ± 2; BMI: 25.9 ± 1.1) and 13 healthy, sedentary control (CON) subjects (age: 62 ± 1; BMI: 25.9 ± 0.4), and to describe relationships between the whole body and local calf muscular exercise capacities within the two groups. Furthermore, this study aimed to compare several histochemical characteristics of the medial gastrocnemius muscle fibres between PAD and CON, and to establish whether these factors were related to the exercise capacities of both groups. Maximal performance on T was 59% lower in the PAD group compared with the CON group, as was performance on C (50%), PF strength (25%), and PF endurance (58%). Compared with CON, PAD patients had a lower estimated calf muscle mass and a slight reduction (10%) in muscle fibre size (p=.14, NS). They also had a lower proportion of type I fibres (PAD: 49%; CON: 62%) that was offset by a greater proportion of type IIA fibres (PAD: 27%; CON: 16%), and a reduction in the capillary contacts per muscle fibre (PAD: 1.63; CON: 2.12) compared with CON. When expressed relative to fibre area there were no differences in capillarisation between PAD and CON; however this index was significantly related to resting and post exercise ABI in the PAD patients. There were no differences in the mixed muscle [glycogen], nor the optical density of glycogen in the individual fibres, between the two groups. PF endurance was poorly predictive of walking performance, and did not correlate with any of the morphological variables in both groups. Calf muscle mass correlated with PF strength (r=.59 - .62), and strength was correlated with T performance (r= .61 - .63) in both groups. In the PAD patients, T performance was correlated with the cross sectional area (n=12, r=.72, p<.05), capillary contacts (n=10, r=.81, p<.05) and glycogen density (n=9, r=.81, p<.05) of type I fibres. This study confirms that a reduction in calf strength, which appears to be mediated through muscle atrophy, plays some role in the reduced exercise capacity of claudicants. While both fibre area and capillary supply seem to be of relevance to the exercise capacity of PAD patients, these two factors are closely linked and further research is required to establish the determinants, and relative importance of both. An important, and possibly limiting role of carbohydrate oxidisation in PAD patients is supported by the strong relationship between type I glycogen stores and whole body exercise capacity.

Dietary fat has long been implicated in the etiology of metabolic and cardiovascular disease, and both the amount of fat and the fatty acid composition of the diet play a role in disease progression. Although national health organizations have set guidelines for the recommended intake of dietary fats, questions remain regarding the optimal dietary lipid profile for maintaining health and improving disease conditions. Whether certain types of fatty acids from plant-based oils can improve metabolic and vascular disease has been studied and debated, but not fully determined. In this study, we investigated the role of dietary fatty acids from plant-based oils, and examined their effects on metabolic and vascular disease parameters. Obese fa/fa Zucker rats were fed a diet containing flaxseed oil, which resulted in smaller adipocytes and decreased adipose tissue T-cell infiltration. Obese-prone Sprague Dawley rats were fed high-fat diets with different proportions of mono- and polyunsaturated fats. Changes were observed in adipose tissue levels of fatty acid synthase, adiponectin and fatty acid receptors GPR41 and GPR43, but other metabolic and inflammatory mediators in adipose tissue and serum remained stable. A systematic review and meta-analysis on the impact of n3 fatty acids on major cardiovascular endpoints showed that little evidence exists to support their role in peripheral arterial disease. Then again, very few studies on this topic have been conducted. To address this research gap, a clinical trial was designed to investigate the effects of a dietary intervention on blood vessel properties in people with peripheral arterial disease. Participants in the Canola-PAD Study consumed 25 g/day of canola oil or a Western diet oil mixture as part of their usual diet for 8 weeks. Although the intervention altered phospholipid fatty acids, vascular function, the lipid profile and inflammatory markers stayed relatively stable. Overall, this research demonstrates that dietary fatty acids from plant-based oils can be immunomodulatory, but at the physiological doses tested they are not potent mediators of functional changes in obesity or vascular physiology. / October 2015

L’artériopathie oblitérante des membres inférieurs (AOMI) est une affection vasculaire obstructive athéroscléreuse. Elle touche 20% des plus de 70 ans. L’ischémie critique des membres inférieurs (ICMI) est le stade ultime et nécessite une revascularisation. La thérapie cellulaire (TC) tente de promouvoir l’angiogenèse chez les patients en impasse thérapeutique. Les cellules souches mésenchymateuses (MSCs) sont un bon candidat, car elles associent des propriétés angiogéniques et immunomodulatrices. L’objectif de cette thèse a été 1), d’évaluer dans un modèle murin d’ischémie de la patte, l’efficacité de deux types de MSCs: les MSCs indifférenciées et les MSCs « endothelial like » (MELs) en les comparant aux cellules dérivées de la moelle osseuse; 2) d’analyser le membre ischémié par spectroscopie Raman.Les MELs et les MSCs ont induit une restauration complète du flux et une amélioration fonctionnelle du membre. Aucune nécrose n’a été signalée après administration des MELs. Histologiquement, les MELs ont induit les taux les plus élevés de néoangiogenèse et de régénération musculaire. Les acquisitions spectrales ont révélé que la spectroscopie Raman peut différencier un membre ischémié d'un membre sain et indique une augmentation du ratio lipide/protide au cours de l’ischémie.Notre étude indique que les MELs de patients ICMI rétablissent le flux sanguin et permettent la réparation musculaire. La spectroscopie Raman peut être utilisée pour évaluer l'ischémie chez les patients atteints d’ICMI. / Peripheral artery disease (PAD) is an atherosclerotic obstructive disease affecting lower limbs arteries. It affects nearly 20% of over 70s. Critical limb ischemia (CLI) is the ultimate stage and requires revascularization. Cell therapy (CT) has been proposed for patients with CLI. Clinical trials were encouraging but failed to establish efficacy. Mesenchymal stem cells (MSCs) may be a better option as they combine angiogenic and immunomodulatory properties. MSCs can be obtained from BMCs of CLI-patients. The aim of this study was first to evaluate, in a murine hindlimb ischemia model, the efficacy of two types of MSCs: undifferentiated mesenchymal stem cells (MSCs) and “endothelial like” MSCs (MELs) in comparison with currently used BMCs. Secondly, the objective was to perform a non-invasive analysis of ischemic limb using Raman Spectroscopy. MELs and MSCs induced complete perfusion restoration whereas BMCs did not. The complete flow recovery was significantly earlier with MELs in comparison with MSCs. Both MSCs and MELs improved functionality more efficiently than BMCs. Interestingly, complete limb salvage was observed in the MELs treated group exclusively. In muscles, MELs induced the highest rate of neoangiogenesis and the best muscle repair as shown by the presence of regenerated myofibers. Spectral acquisitions revealed that Raman spectroscopy can discriminate ischemic limb from healthy limb and can grade ischemia over time.Our study brings evidence that MELs obtained from CLI-patients can restore blood flow and provide muscle repair. Moreover Raman spectroscopy could be used clinically to assess ischemia in CLI-patients.

O aumento da morbimortalidade cardiovascular nos indivíduos com doença arterial periférica (DAP) e claudicação intermitente (CI) se associa a alterações hemodinâmicas, autonômicas, endoteliais, inflamatórias e de estresse oxidativo, que são inerentes ao desenvolvimento da própria doença. O treinamento de caminhada (TC) pode atenuar os processos fisiopatológicos que cursam com a doença, o que precisa ser melhor investigado. Por outro lado, a execução da caminhada até a dor máxima nesses indivíduos provoca episódios de isquemia, que geram alterações nesses processos e promovem sobrecarga cardiovascular. É possível que o TC possa atenuar essas respostas após o esforço máximo, o que também foi pouco investigado. Dessa forma, o objetivo do presente estudo foi verificar, em indivíduos com DAP e CI, o efeito de um TC sobre a função e regulação cardiovasculares, bem como sobre marcadores locais (músculo) e sistêmicos (sangue) de função endotelial, estresse oxidativo e inflamação, avaliados em repouso e após uma caminhada até a dor máxima de claudicação. Para tanto, 32 homens com DAP e CI foram divididos aleatoriamente em dois grupos: TC (n = 16, 2 sessões/sem, 15 séries de 2 min de caminhada na frequência cardíaca do limiar de dor intercaladas com 2 min de pausa passiva) e controle (CO, n =16, 2 sessões/semana, 30 min alongamento). No início e ao final do estudo, os indivíduos realizaram uma caminhada máxima e as seguintes avaliações foram realizadas pré e pós-caminhada: função cardiovascular (pressão arterial - PA, frequência cardíaca - FC, duplo produto - DP); regulação autonômica cardiovascular (variabilidade da FC e da PA e sensibilidade barorreflexa - SBR); função endotelial (óxido nítrico sanguíneo - NO e óxido nítrico sintase muscular - eNOS); estresse oxidativo (catalase - CAT, superóxido dismutase - SOD, peroxidação lipídica - LPO no sangue e no músculo); e inflamação (interleucina-6 - IL-6, proteína C-reativa - PCr, fator de necrose tumoral alfa - TNF-alfa, moléculas de adesão intercelular - ICAM, moléculas de adesão vascular - VCAM no sangue e no músculo). Os dados foram avaliados pela ANOVA de 2 fatores, empregando-se o teste de post-hoc de Newman-Keuls e adotando-se P<0,05 como significante. No repouso, o TC diminuiu a sobrecarga cardiovascular (PA sistólica, PA média, FC e DP) e o balanço simpatovagal cardíaco; aumentou a SBR, a biodisponibilidade de NO, a eNOS e a defesa antioxidante (SOD e CAT no sangue; SOD no músculo), além de reduzir o perfil inflamatório (PCr, ICAM e VCAM no sangue; IL-6 e PCr no músculo) (todos, p<0,05). Em relação à resposta à caminhada máxima, o TC: 1) não modificou o aumento da sobrecarga cardiovascular ao esforço, mas diminuiu a sobrecarga absoluta após o exercício (PA sistólica, PA média e DP); 2) diminuiu a resposta do NO sanguíneo e da eNOS muscular, sem alterar os valores absolutos atingidos após o exercício; 3) não modificou a resposta e os valores absolutos pós-exercício da capacidade antioxidante (SOD e CAT) e do estresse oxidativo (LPO) sistêmicos e locais, mas impediu o aumento da LPO pós-exercício observado no grupo CO; e 4) aumentou a resposta inflamatória sistêmica e local ao exercício (TNF-alfa, ICAM e VCAM no sangue e IL-6, PCr e VCAM no músculo) com manutenção da inflamação sistêmica pós-exercício e redução da inflamação local (VCAM). Em conclusão, em homens com DAP e CI, o TC melhora a modulação autonômica e a função cardiovascular, aumenta a biodisponibilidade de NO e diminui o estresse oxidativo e a inflamação tanto sistêmicos quanto locais. Além disso, o TC, de modo geral, não altera ou mesmo reduz as respostas desses marcadores após uma caminhada até a dor máxima de claudicação / The increase in cardiovascular morbimortality in individuals with peripheral artery disease (PAD) and intermittent claudication (IC) is associated with alterations in cardiovascular function, cardiac autonomic modulation, endothelial function, oxidative stress and inflammation, which are processes inherent to the disease development. Walking training (WT) may attenuate these pathophysiological processes, however, knowledge about these effects of WT is scarce and controversial. On the other hand, in these individuals, a bout of walking promotes ischemic episodes that may exacerbate these processes, leading to cardiovascular overload. WT might attenuate these post-walking responses; however, these effects were also poorly studied. Thus, the aim of the present study was to evaluate, in individuals with PAD and IC, the effects of WT on cardiovascular autonomic modulation and function as well as on blood and muscle markers of endothelial function, oxidative stress and inflammation assessed at rest and after a walking until maximal leg pain. Thirty-two men with PAD and IC were randomly allocated in two groups: WT (n = 16, 2 sessions/week, 15 bouts of 2 min walking at an intensity corresponding to the heart rate of the pain threshold interspersed with 2 min of passive pause) and control (CO, n =16, 2 sessions/week, 30 min of stretching). At the beginning and end of the study, the subjects underwent a maximal walking and the following evaluations were done pre and post-exercise: cardiovascular function (blood pressure - BP, heart rate - HR, rate pressure product - RPP); cardiovascular autonomic modulation (HR and BP variabilities and baroreflex sensitivity - BRS); endothelial function (blood nitric oxide - NO and muscle nitric oxide synthase - eNOS); oxidative stress (catalase - CAT, superoxide dismutase - SOD, lipid peroxidation - LPO measured in blood and muscle); and inflammation (interleukin-6 - IL-6, C-reactive protein - CRP, tumor necrosis factor alpha - TNF-alpha, intercellular adhesion molecules - ICAM, vascular adhesion molecules - VCAM measured in blood and muscle). Data were evaluated by 2-way ANOVA, and Newman-Keuls test was used as a post-hoc. P <0.05 was set as significant. At rest, WT decreased cardiovascular overload (systolic BP, mean BP, HR and RPP) and sympathovagal balance; increased BRS, blood NO, muscle eNOS and antioxidant defence (blood SOD and CAT, and muscle SOD), besides decreasing inflammatory markers (blood CRP, ICAM and VCAM and muscle IL-6 and CRP). Concerning the response after maximal walking, WT: 1) did not change cardiovascular overload increase after the effort, but reduced the absolute post-exercise overload (systolic BP, mean BP and RPP); 2) decreased blood NO and muscle eNOS responses without changing the absolute values achieved after the exercise; 3) did not change systemic and local antioxidant (SOD and CAT) and oxidative stress (LPO) responses as well as post-exercise absolute values; but mitigated the increase in postexercise oxidative stress observed in the CO group; and 4) increased systemic and local inflammatory responses (blood TNF-alpha, ICAM e VCAM and muscle IL-6, PCr e VCAM), but did not change post-exercise absolute systemic inflammation and decreased post-exercise absolute local inflammation (VCAM). In conclusion, in men with PAD and IC, WT improves cardiovascular function and autonomic modulation, increases NO bioavailability and decreases systemic and local oxidative stress and inflammation. In addition, in general, WT does not alter or even reduces these processes responses after a walking until maximal claudication pain

O aumento da morbimortalidade cardiovascular nos indivíduos com doença arterial periférica (DAP) e claudicação intermitente (CI) se associa a alterações hemodinâmicas, autonômicas, endoteliais, inflamatórias e de estresse oxidativo, que são inerentes ao desenvolvimento da própria doença. O treinamento de caminhada (TC) pode atenuar os processos fisiopatológicos que cursam com a doença, o que precisa ser melhor investigado. Por outro lado, a execução da caminhada até a dor máxima nesses indivíduos provoca episódios de isquemia, que geram alterações nesses processos e promovem sobrecarga cardiovascular. É possível que o TC possa atenuar essas respostas após o esforço máximo, o que também foi pouco investigado. Dessa forma, o objetivo do presente estudo foi verificar, em indivíduos com DAP e CI, o efeito de um TC sobre a função e regulação cardiovasculares, bem como sobre marcadores locais (músculo) e sistêmicos (sangue) de função endotelial, estresse oxidativo e inflamação, avaliados em repouso e após uma caminhada até a dor máxima de claudicação. Para tanto, 32 homens com DAP e CI foram divididos aleatoriamente em dois grupos: TC (n = 16, 2 sessões/sem, 15 séries de 2 min de caminhada na frequência cardíaca do limiar de dor intercaladas com 2 min de pausa passiva) e controle (CO, n =16, 2 sessões/semana, 30 min alongamento). No início e ao final do estudo, os indivíduos realizaram uma caminhada máxima e as seguintes avaliações foram realizadas pré e pós-caminhada: função cardiovascular (pressão arterial - PA, frequência cardíaca - FC, duplo produto - DP); regulação autonômica cardiovascular (variabilidade da FC e da PA e sensibilidade barorreflexa - SBR); função endotelial (óxido nítrico sanguíneo - NO e óxido nítrico sintase muscular - eNOS); estresse oxidativo (catalase - CAT, superóxido dismutase - SOD, peroxidação lipídica - LPO no sangue e no músculo); e inflamação (interleucina-6 - IL-6, proteína C-reativa - PCr, fator de necrose tumoral alfa - TNF-alfa, moléculas de adesão intercelular - ICAM, moléculas de adesão vascular - VCAM no sangue e no músculo). Os dados foram avaliados pela ANOVA de 2 fatores, empregando-se o teste de post-hoc de Newman-Keuls e adotando-se P<0,05 como significante. No repouso, o TC diminuiu a sobrecarga cardiovascular (PA sistólica, PA média, FC e DP) e o balanço simpatovagal cardíaco; aumentou a SBR, a biodisponibilidade de NO, a eNOS e a defesa antioxidante (SOD e CAT no sangue; SOD no músculo), além de reduzir o perfil inflamatório (PCr, ICAM e VCAM no sangue; IL-6 e PCr no músculo) (todos, p<0,05). Em relação à resposta à caminhada máxima, o TC: 1) não modificou o aumento da sobrecarga cardiovascular ao esforço, mas diminuiu a sobrecarga absoluta após o exercício (PA sistólica, PA média e DP); 2) diminuiu a resposta do NO sanguíneo e da eNOS muscular, sem alterar os valores absolutos atingidos após o exercício; 3) não modificou a resposta e os valores absolutos pós-exercício da capacidade antioxidante (SOD e CAT) e do estresse oxidativo (LPO) sistêmicos e locais, mas impediu o aumento da LPO pós-exercício observado no grupo CO; e 4) aumentou a resposta inflamatória sistêmica e local ao exercício (TNF-alfa, ICAM e VCAM no sangue e IL-6, PCr e VCAM no músculo) com manutenção da inflamação sistêmica pós-exercício e redução da inflamação local (VCAM). Em conclusão, em homens com DAP e CI, o TC melhora a modulação autonômica e a função cardiovascular, aumenta a biodisponibilidade de NO e diminui o estresse oxidativo e a inflamação tanto sistêmicos quanto locais. Além disso, o TC, de modo geral, não altera ou mesmo reduz as respostas desses marcadores após uma caminhada até a dor máxima de claudicação / The increase in cardiovascular morbimortality in individuals with peripheral artery disease (PAD) and intermittent claudication (IC) is associated with alterations in cardiovascular function, cardiac autonomic modulation, endothelial function, oxidative stress and inflammation, which are processes inherent to the disease development. Walking training (WT) may attenuate these pathophysiological processes, however, knowledge about these effects of WT is scarce and controversial. On the other hand, in these individuals, a bout of walking promotes ischemic episodes that may exacerbate these processes, leading to cardiovascular overload. WT might attenuate these post-walking responses; however, these effects were also poorly studied. Thus, the aim of the present study was to evaluate, in individuals with PAD and IC, the effects of WT on cardiovascular autonomic modulation and function as well as on blood and muscle markers of endothelial function, oxidative stress and inflammation assessed at rest and after a walking until maximal leg pain. Thirty-two men with PAD and IC were randomly allocated in two groups: WT (n = 16, 2 sessions/week, 15 bouts of 2 min walking at an intensity corresponding to the heart rate of the pain threshold interspersed with 2 min of passive pause) and control (CO, n =16, 2 sessions/week, 30 min of stretching). At the beginning and end of the study, the subjects underwent a maximal walking and the following evaluations were done pre and post-exercise: cardiovascular function (blood pressure - BP, heart rate - HR, rate pressure product - RPP); cardiovascular autonomic modulation (HR and BP variabilities and baroreflex sensitivity - BRS); endothelial function (blood nitric oxide - NO and muscle nitric oxide synthase - eNOS); oxidative stress (catalase - CAT, superoxide dismutase - SOD, lipid peroxidation - LPO measured in blood and muscle); and inflammation (interleukin-6 - IL-6, C-reactive protein - CRP, tumor necrosis factor alpha - TNF-alpha, intercellular adhesion molecules - ICAM, vascular adhesion molecules - VCAM measured in blood and muscle). Data were evaluated by 2-way ANOVA, and Newman-Keuls test was used as a post-hoc. P <0.05 was set as significant. At rest, WT decreased cardiovascular overload (systolic BP, mean BP, HR and RPP) and sympathovagal balance; increased BRS, blood NO, muscle eNOS and antioxidant defence (blood SOD and CAT, and muscle SOD), besides decreasing inflammatory markers (blood CRP, ICAM and VCAM and muscle IL-6 and CRP). Concerning the response after maximal walking, WT: 1) did not change cardiovascular overload increase after the effort, but reduced the absolute post-exercise overload (systolic BP, mean BP and RPP); 2) decreased blood NO and muscle eNOS responses without changing the absolute values achieved after the exercise; 3) did not change systemic and local antioxidant (SOD and CAT) and oxidative stress (LPO) responses as well as post-exercise absolute values; but mitigated the increase in postexercise oxidative stress observed in the CO group; and 4) increased systemic and local inflammatory responses (blood TNF-alpha, ICAM e VCAM and muscle IL-6, PCr e VCAM), but did not change post-exercise absolute systemic inflammation and decreased post-exercise absolute local inflammation (VCAM). In conclusion, in men with PAD and IC, WT improves cardiovascular function and autonomic modulation, increases NO bioavailability and decreases systemic and local oxidative stress and inflammation. In addition, in general, WT does not alter or even reduces these processes responses after a walking until maximal claudication pain

Introduction Hypertension occurs when there is persistent increase in the pressure of blood vessels in the body; this condition affects about 75 million people in the United States (U.S.). Hypertension is a major risk factor for Peripheral Artery Disease (PAD). PAD is a narrowing of the peripheral arteries in legs, stomach, arms and head regions of the body except the heart. Research has shown that hypertension can be life-threatening for patients with PAD. Moreover, research supports an evidence of a low threshold for blood pressure treatment in patients with PAD. Additionally, current American Heart Association guidelines recommend treating hypertension in patients with PAD to reduce the risk of other cardiovascular disease (CVD) comorbidities. In Central Appalachia, the rate of hypertension and the corresponding risk factors is higher than the national average. As such, this study examined the multiple risk factors of hypertension in patients with PAD within the Central Appalachian region. Method The study population consists of patients diagnosed with PAD in a large health system in Central Appalachia from 2008 to 2018. We extracted 13,455 patients with PAD from Electronic Medical Records (EMR) system using ICD- 9 and ICD-10 codes. The outcome variable of the study was hypertension in PAD patients. Explanatory variables included gender, age, and cardiovascular risk factors (myocardial infarction (MI), Body Mass Index (BMI), diabetes mellitus, smoking status, low-density lipoprotein, high-density lipoprotein, triglycerides, and hypercholesterolemia). Multivariable logistic regression was performed to assess the association between risk factors of hypertension in male and female PAD patients. All analyses were performed using SPSS version 24. RESULTS Of the total PAD patients in the study, 45.8% were females and 54.2% were males. Of these patients, 79.1%, 45.7% and 22.6% had hypertension, diabetes and a history of MI, respectively. Upon stratifying based on gender, the odds of hypertension in PAD female patients with a history of MI was approximately 5.4 times (OR: 5.4, CI : 1.80-16.21) and 2.6 times higher with diabetes (OR: 2.6, CI: 1.43-4.83). Whereas in PAD male patients, the odds of hypertension was 3.9 (OR: 2.6, CI: 1.61-9.21) and 2.6 times (OR: 2.6, CI: 1.43-4.83) higher in those with a history of MI and diabetes, respectively. Stratifying by MI, the odds of hypertension in PAD increased by 2.8 times in patients with diabetes (OR: 2.6, CI: 1.75-4.49). Stratifying by diabetes showed that the odds of hypertension in PAD increased by 4.7 times in patients with MI (OR: 4.7, CI: 1.32-17.07). CONCLUSION The study showed that odds of hypertension in PAD patients is increased in the presence of diabetes and history of MI in both genders. Therefore, controlling diabetes and myocardial infarction will have the greatest impact in reducing the likelihood of hypertension leading to decreased morbidity and mortality in patients with PAD.

Background: Peripheral arterial disease (PAD), as a consequence of atherosclerosis in the arteria of the limbs, affects one of ten Swedes older than 65. PAD can develop slowly and silently, and involves an increased risk for cardiac infarction and stroke. Measurement of the patient´s ankle blood pressure and calculation of the ankle-brachial index is an evidence-based method to discover PAD. Objective: To investigate how district nurses and general practitioners perceive this method of examination and experience possible obstacles to why it is not more commonly applied at primary health care centres. Method: Data collected by semi-structured interviews have been processed by qualitative content analysis with a manifest onset. Results: The participants described a lack of routine for the measurement of ankle blood pressure at their health care centres. In their experience the cooperation of district nurses and general practitioners was characterized by insufficient information and unclear roles. Conclusion: As a consequence of lacking routines and indistinct roles at the health care centres, measurement of ankle blood pressure was not always performed as indicated in the guidelines. More knowledge and established routines could have led to better care for patients with PAD. / Bakgrund: Perifer artärsjukdom till följd av ateroskleros (åderförfettning eller åderförkalkning) i benens pulsådror drabbar en av tio svenskar över 65 år. Sjukdomen, som länge kan vara symtomfri, medför en ökad risk för hjärtinfarkt och stroke. Ankeltrycksmätning och beräkning av ankelbrakialindex är en evidensbaserad metod för att upptäcka perifer artärsjukdom. Syfte: Att beskriva hur distriktssköterskor och distriktsläkare uppfattade mätning av ankeltryck, beräkning av ankelbrakialindex och eventuella hinder för att använda metoden inom primärvården. Metod: Data samlades in med hjälp av semistrukturerade intervjuer och analyserades med hjälp av kvalitativ innehållsanalys med manifest ansats. Resultat: Informanterna upplevde att rutiner för att mäta ankeltryck saknades på deras vårdcentraler. I stället var det upp till informanterna själva att avgöra om och när de skulle mäta. Samarbetet kring patienterna mellan distriktsläkare och distriktssköterskor präglades av bristfällig information och oklara roller. Slutsats: Avsaknaden av rutiner och en otydlig rollfördelning ledde till att ankeltryck inte alltid mättes på de patienter som borde ha undersökts med hjälp av metoden. Bättre kunskaper och rutiner för ankeltrycksmätning i primärvården skulle kunna leda till säkrare vård för patienter med perifer artärsjukdom.

Περισσότεροι από 20 εκατομμύρια άνθρωποι στην Ευρώπη πάσχουν από περιφερική αποφρακτική αρτηριοπάθεια των κάτω άκρων (ΠΑΑΚΑ) και ο σακχαρώδης διαβήτης αποτελεί πλέον διαπιστωμένα έναν από τους ανεξάρτητους παράγοντες κινδύνου της νόσου. Ο μηριαίο-ιγνυακός άξονας είναι γνωστός ως μια ιδιαίτερα “εχθρική” ανατομική περιοχή, όσον αφορά στην ενδαγγειακή αντιμετώπιση της ΠΑΑΚΑ, καθώς παρά τα υψηλά ποσοστά άμεσης τεχνικής επιτυχίας, παρουσιάζει επίσης υψηλά ποσοστά κλινικής υποτροπής και επανεπεμβάσεων λόγω του φαινομένου της επαναστένωσης. Η κρυοπλαστική έχει προταθεί ως μια νέα μέθοδος αντιμετώπισης της ΠΑΑΚΑ του μηριαίο-ιγνυακού άξονα, παρουσιάζοντας ικανοποιητικά αρχικά αποτελέσματα. Σκοπός της συγκεκριμένης ερευνητικής εργασίας ήταν τόσο η κλινική μελέτη των άμεσων και μακροχρόνιων αποτελεσμάτων της εμπορικά διαθέσιμης κρυοπλαστικής, όσον αφορά στην αντιμετώπιση της ΠΑΑΚΑ του μηριαίο-ιγνυακού άξονα διαβητικών ασθενών, όσο και η πειραματική εφαρμογή της σε in vivo αρτηριακό μοντέλο κονίκλων, συγκριτικά με την συμβατική αγγειοπλαστική. Το διπλό αυτό επιστημονικό πρωτόκολλο, απέφερε τα πρώτα μακροχρόνια αγγειογραφικά και κλινικά δεδομένα της τυχαιοποιημένης σύγκρισης μεταξύ της κρυοπλαστικής και της συμβατικής αγγειοπλαστικής στην συγκεκριμένη ανατομική περιοχή, καθώς και τα πρώτα in vivo αποτελέσματα της σύγκρισης των δύο μεθόδων, αλλά και της διπλής εφαρμογής της κρυοπλαστικής στο αρτηριακό τοίχωμα. Τα κλινικά αποτελέσματα δεν επαλήθευσαν την ανωτερότητα της κρυοπλαστικής έναντι της συμβατικής αγγειοπλαστικής, καθώς η πολύπαραγοντική Cox ανάλυση ανίχνευσε μεγαλύτερο ποσοστό κινδύνου όσον αφορά στην απώλεια της πρωτογενούς βατότητας και στην διενέργεια επανεπεμβάσεων, ενώ η διωνυμική Kaplan-Meyer ανάλυση προέβλεψε σημαντικά μεγαλύτερο ποσοστό επαναστένωσης στα 3 έτη. Εν αντιθέσει, τα αποτελέσματα του πειραματικού πρωτοκόλλου εξακρίβωσαν μεγαλύτερα ποσοστά απόπτωσης των λείων μυϊκών κυττάρων του μέσου χιτώνα στην ομάδα της κρυοπλαστικής, συγκριτικά με την συμβατική αγγειοπλαστική. Επίσης η διπλή εφαρμογή της κρυοπλαστικής απεδείχθη ασφαλής, με χαμηλό βαθμό αρτηριακού τραυματισμού και φλεγμονής. Παρά ταύτα η διπλή εφαρμογή δεν απέφερε ποσοτική αύξηση της απόπτωσης των λείων μυϊκών κυττάρων του μέσου χιτώνα, συγκριτικά με την μονή εφαρμογή. Τα αποτελέσματα της συγκεκριμένης επιστημονικής εργασίας οδηγούν στο συμπέρασμα ότι πράγματι η κρυοπλαστική αποτελεί μια ελάχιστα τραυματική μέθοδο αγγειοπλαστικής, η οποία επάγει την απόπτωση των λείων μυϊκών κυττάρων, χωρίς να προκαλεί νέκρωση των κυτταρικών στοιχείων του αρτηριακού τοιχώματος, αλλά η βελτιστοποίηση του συστήματος αποτελεί αναγκαιότητα για την περαιτέρω κλινική της εφαρμογή. / Peripheral obstructive arterial disease (PAOD) represents a pathology affecting over 20 million people in Europe and diabetes mellitus (DM) has been long recognized as an independent risk factor of PAOD. The main artery affected by the disease is the femoropopliteal axis, which constitutes a particularly hostile territory, regarding the percutaneous endovascular treatment, due to the disappointedly high percentages of restenosis and clinically driven repeated procedures. Cryoplasty has been proposed as a novel method of endovascular treatment of the femoropopliteal axis, with acceptable initial results. This particular scientific research was aiming in the clinical investigation of the immediate and long term results of the commercially available cryoplasty system in the femoropopliteal artery of patients suffering from DM, as well as the study of cryoplasty application in an experimental in vivo animal model, compared to conventional balloon angioplasty (COBA). This double scientific protocol reported the first long-term angiographic and clinical data, regarding the randomized comparison of cryoplasty and COBA in the specific anatomical region and also the first results from the direct comparison of the single and double PolarCath application versus a conventional balloon catheter, in an in vivo arterial animal model. Cryoplasty was not proven superior to COBA, as the multivariable Cox statistical model detected cryoplasty as an independent predictor of reduced primary patency and elevated repeated clinically driven procedures, while the bivariable Kaplan-Meyer estimated significantly higher restenosis rate in the cryoplasty group, up to 3 years follow-up. On the other hand, the results from the in vivo application of cryoplasty detected superior smooth muscle cells (SMC) apoptotic rates, compared to the control group. The double application of cryoplasty on the arterial wall was safe as it resulted in low grade arterial barotrauma and inflammation scores. However, the double application of cryoplasty was not able to induce superior rates of apoptosis of the SMC, compared to the single application. The results herein reported, suggest that although cryoplasty can be considered a safe and minimally traumatic method of angioplasty, which induces apoptosis and not necrosis of the SMC, the optimization of the system is fundamental, in order to be further applied in every day clinical practice.

Introduction Hypertension occurs when there is persistent increase in the pressure of blood vessels in the body; this condition affects about 75 million people in the United States (U.S.). Hypertension is a major risk factor for Peripheral Artery Disease (PAD). PAD is a narrowing of the peripheral arteries in legs, stomach, arms and head regions of the body except the heart. Research has shown that hypertension can be life-threatening for patients with PAD. Moreover, research supports an evidence of a low threshold for blood pressure treatment in patients with PAD. Additionally, current American Heart Association guidelines recommend treating hypertension in patients with PAD to reduce the risk of other cardiovascular disease (CVD) comorbidities. In Central Appalachia, the rate of hypertension and the corresponding risk factors is higher than the national average. As such, this study examined the multiple risk factors of hypertension in patients with PAD within the Central Appalachian region. Method The study population consists of patients diagnosed with PAD in a large health system in Central Appalachia from 2008 to 2018. We extracted 13,455 patients with PAD from Electronic Medical Records (EMR) system using ICD- 9 and ICD-10 codes. The outcome variable of the study was hypertension in PAD patients. Explanatory variables included gender, age, and cardiovascular risk factors (myocardial infarction (MI), Body Mass Index (BMI), diabetes mellitus, smoking status, low-density lipoprotein, high-density lipoprotein, triglycerides, and hypercholesterolemia). Multivariable logistic regression was performed to assess the association between risk factors of hypertension in male and female PAD patients. All analyses were performed using SPSS version 24. RESULTS Of the total PAD patients in the study, 45.8% were females and 54.2% were males. Of these patients, 79.1%, 45.7% and 22.6% had hypertension, diabetes and a history of MI, respectively. Upon stratifying based on gender, the odds of hypertension in PAD female patients with a history of MI was approximately 5.4 times (OR: 5.4, CI : 1.80-16.21) and 2.6 times higher with diabetes (OR: 2.6, CI: 1.43-4.83). Whereas in PAD male patients, the odds of hypertension was 3.9 (OR: 2.6, CI: 1.61-9.21) and 2.6 times (OR: 2.6, CI: 1.43-4.83) higher in those with a history of MI and diabetes, respectively. Stratifying by MI, the odds of hypertension in PAD increased by 2.8 times in patients with diabetes (OR: 2.6, CI: 1.75-4.49). Stratifying by diabetes showed that the odds of hypertension in PAD increased by 4.7 times in patients with MI (OR: 4.7, CI: 1.32-17.07). CONCLUSION The study showed that odds of hypertension in PAD patients is increased in the presence of diabetes and history of MI in both genders. Therefore, controlling diabetes and myocardial infarction will have the greatest impact in reducing the likelihood of hypertension leading to decreased morbidity and mortality in patients with PAD.

Introduction Lipoprotein(a) (Lp(a)) and oxidized LDL (oxLDL) are circulating lipoproteins known to promote development of atherosclerosis. LDL can be oxidized in several ways, including enzymatic oxidation by myeloperoxidase (MPO). The knowledge regarding these biomarkers in men and women with different presentations of peripheral arterial disease (PAD) is scarce. Aim To investigate sex differences in plasma levels of MPO, Lp(a) and oxLDL in patients undergoing open vascular surgery. A secondary aim was to elucidate how indication for surgery, risk factors and comorbidity influenced the levels of lipid markers. Methods A multicenter observational study done within the framework of an ongoing study targeting atherosclerosis, where lipids and inflammation are studied in patients undergoing open vascular surgery for either PAD (intermittent claudication (IC) or critical limb ischemia (CLI)) or carotid artery stenosis, having an ankle brachial pressure index &lt;0.9 or &gt;1.4. Participants were included 2019-2020, with blood samples collected immediately before surgery. Results A total of 30 men and 26 women were included. The indication for surgery was CLI (50.0%), IC (30.4%) and carotid stenosis (19.6%). Women and men displayed similar levels of Lp(a), MPO and oxLDL. Lp(a) was lower among CLI patients as compared to IC in univariate (P=0.038) but not in multivariate analysis. Oxidized LDL levels and LDL, Lp(a) and cholesterol correlated significantly. Conclusions There were no statistically significant differences in lipid markers between sexes. Levels of Lp(a) differed between the surgical indication groups and were lowest among the more severely diseased patients (CLI). Our findings need further evaluation in larger cohorts, taking effects of lipid-lowering therapies into consideration.