Submitted by Rosivalda Pereira (mrs.pereira@ufma.br) on 2017-09-29T17:19:20Z No. of bitstreams: 1 IaraNogueira.pdf: 92869 bytes, checksum: 5e68638ca4fbe0f7a83413724c91dec2 (MD5) / Made available in DSpace on 2017-09-29T17:19:20Z (GMT). No. of bitstreams: 1 IaraNogueira.pdf: 92869 bytes, checksum: 5e68638ca4fbe0f7a83413724c91dec2 (MD5) Previous issue date: 2017-05-25 / Fundação de Amparo à Pesquisa e ao Desenvolvimento Científico e Tecnológico do Maranhão / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Menopause is a physiological process that affects women during their late 40s or early 50s, but it has substantial health consequences, varying from disturbances in the lipid and glucose metabolism to changes in sleep, increasing exposure to cardiovascular disease. The aim of this study was to analyze the lipid profile and cardiovascular risk in pre and post menopause, in order to better understand the possible mechanisms that increase cardiovascular risks after menopause. It was a cross-sectional analytical study, including evaluated 184 women aged to 40 to 65 years. Socio-demographic, clinical, anthropometric and laboratory data were obtained as well as comorbidities, such as diabetes, dyslipidemia, hypertension and metabolic syndrome. The stratification of cardiovascular risk in 10 years was performed using the Framingham equation and the overall risk score. A total of 40 participants blood samples of this total were randomly selected for serum lipidic analysis, using mass spectrometry. Participants mean aged of 50 (SD 6.8) years and 54.8% were defined as postmenopausal. From the Framingham score, most women were classified as low risk, with 95.1% frequency for cardiovascular disease in 10 years in premenopausal women and 74.5% in those postmenopausal, despite the high percentage of risk factors, such dyslipidemia (72.6%), metabolic syndrome (50%), insulin resistance (50.9%) and diabetes (16.7%) in postmenopausal. Stratification by the global risk score was more adequate, that is, 64.6% of premenopausal women and 29.4% of postmenopausal women were classified as low risk, whereas 22% and 62.8% were in the high risk category, respectively. In lipidic analysis, lipid species were found to have increased concentrations in postmenopausal women, with the most notable being ceramides (N.C23: 0.Cer; N.C23:0(OH).Cer and N.C24:0(OH).Cer) with Fold Change of 1.68, 1.59 and 1.58, respectively. It was also observed that 14 metabolites showed a significant difference between pre and post menopause, mainly ceramide species. Strong and positive correlations were identified between several metabolites with fasting glucose, glycated hemoglobin, total cholesterol, LDL and triglycerides. Highlight the associations between the species ceramides (N.C10:0.Cer) and lysophosphatidylethanolamine (LPE.a.C18:0) with fasting glucose (r = 0.83 and r = 0.73, p< 0.05 , respectively) and with glycated hemoglobin (r = 0.81 and r = 0.75, p <0.05, respectively). The data obtained allowed us to conclude that postmenopausal women h, ad a CVD risk that was approximately three times higher than in premenopausal women, and that the Framingham score seemed to underestimate cardiovascular risk in the climacteric, whereas the overall score stratified more adequately once which was consistent with the CVD risk factors observed in this population. However, the main findings of this study were the important lipid changes detected in postmenopausal women, especially in the class ceramides, as well as correlations with classical glycolic and lipid markers that may be useful to investigate diseases associated with this phase. / A menopausa constitui um processo fisiológico que acomete as mulheres entre 40 e 50 anos, porém traz consequências substanciais para a saúde, que variam de distúrbios no metabolismo lipídico e glicídico a alterações no sono, aumentando a exposição para as doenças cardiovasculares. Esta pesquisa teve como objetivo analisar o perfil lipidômico e o risco cardiovascular na pré e pós menopausa, para melhor entender os possíveis mecanismos que aumentam os riscos cardiovasculares após a menopausa. Foi uma pesquisa transversal analítica, que foram avaliadas 184 mulheres, com idade entre 40 e 65 anos. Dados sociodemográficos, clínicos, antropométricos e exames laboratoriais foram obtidos, bem como informações sobre comorbidades, como diabetes, dislipidemia, hipertensão e síndrome metabólica. A estratificação do risco cardiovascular em 10 anos foi realizada utilizando a equação de Framingham e o escore global de risco. Do total das participantes, foram selecionadas aleatoriamente, 40 amostras sanguíneas, para a análise lipidômica, utilizando a técnica de espectrometria de massa. As participantes tinham uma média de idade de 50 anos (DP 6,8), na qual 55% delas estavam na pós-menopausa. Pelo escore de Framingham, a maioria das mulheres foram classificadas em baixo risco, sendo que na pré menopausa a frequência foi de 95,1% e na pós menopausa de 74,5% para doença cardiovascular em 10 anos, apesar do percentual elevado dos fatores de risco, como dislipidemia (72,6%), síndrome metabólica (50%), resistência insulínica (50,9%) e diabetes (16,7%), na pós menopausa. Já a estratificação pelo escore global de risco mostrou que 64,6% das mulheres na pré-menopausa e 29,4% na pós-menopausa foram classificadas como baixo risco, enquanto que 22% e 62,8% estavam na categoria de alto risco, respectivamente. Na análise lipidômica, verificou-se que espécies lipídicas apresentavam concentrações aumentadas na pós menopausa, destacando-se as ceramidas (N.C23:0.Cer; N.C23:0(OH).Cer e N.C24:0(OH).Cer) com Fold Change de 1,68, 1,59 e 1,58, respectivamente. Observou-se também que 14 metabólitos apresentaram diferença significativa entre pré e pós menopausa, principalmente espécies de ceramidas. Foram identificadas correlações fortes e positivas entre vários metabólitos com glicemia em jejum, hemoglobina glicada, colesterol total, LDL e triglicerídeos. Destacamse as associações entre as espécies de ceramidas (N.C10:0.Cer) e lisofosfatidiletanolamina (LPE.a.C18:0) com a glicemia em jejum (r=0,83 e r=0,73; p< 0,05, respectivamente) e com a hemoglobina glicada (r=0,81 e r=0,75; p< 0,05, respectivamente). Os dados obtidos nos permitiram concluir que as mulheres na pós menopausa apresentavam um risco para DCV aproximadamente três vezes maior que na pré menopausa e que o escore de Framingham parece subestimar o risco cardiovascular no climatério, enquanto que o escore global estratifica mais adequadamente, uma vez que foi condizente com os fatores de risco para DCV observados nesta população. Mas, o principal achado deste estudo foram as importantes alterações nos lipídeos detectadas na pós menopausa, especialmente na classe das ceramidas, além das correlações com marcadores glicídicos e lipídicos clássicos que poderão ser úteis para investigar doenças associadas a esta fase.

Submitted by Marcos Anselmo (marcos.anselmo@unipampa.edu.br) on 2016-09-22T12:57:22Z No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) PatriciaMaurer.pdf: 1214978 bytes, checksum: 59751fb7a14586f406187c0afea9a8ef (MD5) / Approved for entry into archive by Marcos Anselmo (marcos.anselmo@unipampa.edu.br) on 2016-09-22T12:58:09Z (GMT) No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) PatriciaMaurer.pdf: 1214978 bytes, checksum: 59751fb7a14586f406187c0afea9a8ef (MD5) / Made available in DSpace on 2016-09-22T12:58:09Z (GMT). No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) PatriciaMaurer.pdf: 1214978 bytes, checksum: 59751fb7a14586f406187c0afea9a8ef (MD5) Previous issue date: 2015-07-24 / A população negra apresenta elevado risco cardiometabólico, contudo em estudos populacionais a incidência de síndrome metabólica (SM) nesta população é baixa. Neste contexto, parece existir um paradoxo relacionado aos critérios diagnósticos da SM, o que faz com que a presença da mesma seja subestimada em negros. Esta condição traz consigo a necessidade da busca de marcadores mais fidedignos das condições patológicas e do risco cardiometabólico destes indivíduos. Um possível biomarcador é o óxido nítrico (NO), cuja dosagem de metabólitos como nitrito/nitrato (NOx) tem se mostrado associada a alguns critérios da SM, como obesidade e diabetes, entretanto a literatura carece de trabalhos mais específicos para avaliar se níveis alterados de óxido nítrico estão associados com alterações metabólicas e doenças cardiovasculares na população negra. O objetivo deste estudo foi analisar os níveis de NOx como marcador de alterações cardiometabólicas em afrodescendentes, bem como sua relação com parâmetros laboratoriais na população negra. Participaram do estudo 202 indivíduos autodeclarados negros, a maioria mulheres, com idade média de 45 anos. A avaliação antropométrica demonstrou que a maioria da população estudada estava com IMC médio classificado como obesidade grau 1 e com cintura abdominal alterada. A SM foi verificada em 61% da amostra. Os níveis de nitrito/nitrato foram distribuídos em percentis, o percentil 50%=122,3μmol/L foi escolhido como ponto de corte. Valores de NOx<122,3 μmol/L foram associados com maiores Índices de Massa Corporal (p=0,015), circunferência abdominal (p=0,037) e circunferência de quadril (p=0,040). Quanto aos critérios bioquímicos, o NOx associou-se significativamente aos níveis de glicose (p=0049), triglicerídeos (p=0,046), albumina (p=0,034), ácido úrico (p=0,019) e uréia (p=0,052). Na avaliação inflamatória e de estresse oxidativo, apenas a carbonilação de proteínas (p=0,002) foi associada ao NOx, em que o dano foi maior nos indivíduos que tinham valores de NOx menor do que o percentil 50%. Não houve nenhuma associação entre o NOx e o perfil hematológico. Por estar relacionado principalmente com obesidade, dislipidemias, glicose e triglicerídeos, o NOx foi considerado um bom preditor de risco cardiometabólico na população negra, principalmente de progressão de doença, além de ser um teste adaptado facilmente à rotina laboratorial e possível de ser programado em analisadores automáticos e semi-automáticos, necessitando de pouca preparação da amostra. / The black population has a high cardiometabolic risk, however low incidence of metabolic syndrome (MetS). In this context, there seems to be a paradox related to the diagnostic criteria of MetS, which makes the presence of the same is underestimated in blacks. This condition shows the need to look for a more reliable markers of actual pathological conditions and cardiometabolic risk of these individuals. A possible marker is nitric oxide (NO). The dosage metabolic nitrite/nitrate (NOx) have been shown to be associated with certain criteria of the metabolic syndrome, such as obesity and diabetes, however the literature lacks more specific studies to assess whether altered levels of nitric oxide are associated with metabolic and cardiovascular disease among blacks. The aim of this study was to analyze the NOx levels as a marker of cardiometabolic alterations in Brazilian blacks, as well as its relationship with anthropometric, biochemical, inflammatory and oxidative stress in the black population. The study included 202 self-declared black people, mostly women, average age 45 years. Anthropometric assessment showed that most of the study population had an average BMI classified as grade 1 obesity and altered waist circumference. The metabolic syndrome was found in 61% of the sample. NOx levels were distributed in percentiles, the 50% percentile = 122,3μmol / L was chosen as the cutoff point. NOx values <122.3 μmol/L were associated with higher body mass index (p=0.01), waist circumference (p=0.03) and hip circumference (p=0.04). As to biochemical criteria, the NOx was significantly correlated to blood glucose levels (p=0.04), triglycerides (p=0.04), albumin (p=0.03), uric acid (p=0.01) and urea (p=0.05). In inflammatory and oxidative stress assessment, only protein carbonylation (p<0.01) was associated with the NOx, in which the damage was greater in subjects who had NOx values lower than the 50% percentile. There was no association between NOx and the blood profile. To be mainly related to obesity, dyslipidemia, glucose and triglycerides, the NOx was considered a good predictor of cardiometabolic risk in black population, mainly of disease progression as well as being an adapted easily to laboratory test routine and can be programmed in analyzers automatic and semi-automatic, requiring little sample preparation.

A Doença de Alzheimer (DA) vem apresentando aumento progressivo, sendo a causa de demência mais comum nos idosos (acima de 60 anos). Diante disso, há preocupação com alterações do estado de saúde dos cuidadores que compreendem na sua maioria familiares. Cuidar dos pacientes com demência por Doença de Alzheimer pode levar ao estresse crônico e má qualidade de vida. O presente estudo teve como objetivo avaliar fatores de risco cardiovascular, cognição e humor em cuidadoras idosas de pacientes com demência por Doença de Alzheimer, comparando-as com as não cuidadoras. As cuidadoras foram selecionadas por meio da revisão de prontuários do Hospital das Clínicas e do Centro de Saúde Escola da FMRP-USP. As idosas do grupo controle foram selecionadas na mesma área de moradia das idosas cuidadoras. Todas as participantes assinaram o Termo de Consentimento Livre e Esclarecido. Foram realizadas visitas previamente agendadas na casa de todas as participantes. Critérios de exclusão: diabetes; neoplasias malignas e doenças autoimunes, além de outras doenças debilitantes. Foram avaliadas idade, escolaridade, peso, altura, circunferência abdominal e Indice de Massa corpórea (IMC). Foi realizada avaliação laboratorial: dosagem de insulina de jejum; glicemia de jejum; colesterol total e HDL; triglicérides; creatinina; ureia; sódio; potássio; cálcio e TSH. Além disso, foi feita a avaliação da pressão arterial (PA) em domicílio pela pesquisadora e com a Medida Residencial de Pressão Arterial (MRPA), além da avaliação da cognição e humor, com a Escala de Depressão Geriátrica (EDG), Mini Exame do Estado Mental (MEEM) e Mini International Neuropsychiatric Interview (M.I.N.I.). A análise estatística foi realizada com o Teste Quiquadrado, Teste \"t\" de Student, Mann-Whiney e regressão logística simples e múltipla para a estimação do Odds Ratio bruto e ajustado (ORA). Foram avaliadas 62 idosas, sendo 31 cuidadoras de pacientes com Doença de Alzheimer e 31 do grupo controle. Verificou-se que os níveis de colesterol total foram mais elevados em idosas cuidadoras. Não houve diferenças entre os valores de PA sistólica e diastólica entre os grupos em relação às medidas realizadas pela pesquisadora e com a MRPA. De acordo com os resultados, as idosas cuidadoras apresentaram rastreio positivo para depressão em 58%, enquanto que o grupo controle apresentou apenas 16% (ORA=6,62, p<0,01). Em relação ao diagnóstico feito pelo M.I.N.I, 38,7% das cuidadoras apresentaram episódio depressivo, sendo superior ao controle (9,7%) (ORA=5,42, p=0,02). Verificouse que 35,5% das cuidadoras apresentaram transtorno de ansiedade diagnosticado, com 16% no grupo controle (ORA=4,79, p=0,03). A presença do companheiro interferiu para que as cuidadoras apresentassem mais transtorno de ansiedade (p=0,04). Não houve diferença entre a cognição dos grupos pela avaliação do MEEM. Cuidadoras idosas de pacientes dementados com Doença de Alzheimer apresentaram níveis de colesterol mais elevados, mais episódios depressivos e mais transtorno de ansiedade do que as não cuidadoras. A presença do companheiro interferiu para que apresentassem mais transtorno de ansiedade / Alzheimer´s disease (AD) has shown a progressive increase in incidence, being the most common cause of dementia in the older individuals (above 60 years old). Therefore, there is concern with health status change in caregivers, who are mostly relatives. Taking care of AD patients with dementia can lead to chronic stress and poor quality of life. This study aimed to evaluate cardiovascular risk factors, cognition and mood in older caregivers of patients with AD dementia, comparing them with non-caregivers. The caregivers were selected through the review of the Hospital\'s medical records and School Health Center of FMRP-USP. Control group of elderly women were selected in the same housing area of older caregivers. All participants signed a consent form. Visits were previously scheduled and were at the home of all participants. Exclusion criteria: diabetes; malignancies and autoimmune diseases, and other debilitating diseases. Were evaluated: age, education, weight, height, waist circumference and body mass index (BMI). Laboratory testing was performed: fasting insulin; fasting glucose; Total and HDL cholesterol; triglycerides; creatinine; urea; sodium; potassium; calcium and TSH. In addition, blood pressure (BP) evaluation was made at home by the researcher and by the Home Blood Pressure Monitoring (HBPM), and the assessment of cognition and mood, with the Geriatric Depression Scale (GDS), Mini Exam Mental State Examination (MMSE) and Mini International Neuropsychiatric Interview (MINI). Statistical analysis was performed with Chi-square test, test \"t\" test, Mann-whiney and multiple logistic regression and simple to estimate the gross and adjusted Odds Ratio (AOR). 62 older women were assessed, 31 caregivers of demented AD patients and 31 control group It was found that the total cholesterol levels were higher in elderly caregivers (AOR = 3.57, p = 0.03). There was no difference between the systolic and diastolic values between the groups in relation to the measures carried out by the researcher and HBPM. According to the results, older caregivers had a positive screening for depression in 58%, while the control group showed only 16% (AOR = 6.62, p <0.01). Regarding the diagnosis made by M.I.N.I, 38.7% of caregivers had depressive episode, higher than the control (9.7%) (AOR = 5.42, p = 0.02). It was found that 35.5% of caregivers had diagnosis of anxiety disorder, with 16% in the control group (AOR = 4.79, p = 0.03). The presence of the companion interfered, so that the caregivers presented more anxiety disorder (p = 0.04). There was no difference between cognition groups by assessing the MMSE. Concluding, caregivers of patients with AD have higher cholesterol levels, more depressive episodes and anxiety disorder than non-caregivers. The presence of the companion interfered to submit more anxiety disorder

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

Estrés oxidativo e inflamación parecen jugar un papel importante en el proceso de envejecimiento relacionado con la disfunción del sistema cardiovascular humano. Hábitos de vida tales como fumar, consumo de alcohol y ejercicio físico, pueden alterar el estado redox de los tejidos y afectar la relación de los marcadores de estrés oxidativo con la edad. Se requiere Información sobre el estado oxidativo de las poblaciones humanas para verificar la función de daño oxidativo en el envejecimiento y los cambios relacionados con el sistema cardiovascular, con el fin de identificar cuáles son los factores de riesgo cardiovascular más influyentes en el daño oxidativo asociado al envejecimiento y el papel de la dieta y el estilo de vida en esta relación. Este estudio se realizó en una población de 160 personas sanas o con patología leve tratada y compensada, distribuidos uniformemente en un rango de edad de 16 a 84 años. Lo datos recogidos de cada paciente fueron; antropométricos, bioquímica general, personales, dietéticos y se determinó la concentración de variables relacionadas con el estrés oxidativo, inflamación y/o riesgo cardiovascular: Mieloperoxidasa (MPO), Homocisteina, Proteína C Reactiva (PCR) ultrasensible y Malondialdehido (MDA). Resultados. La edad se correlaciona con numerosos marcadores de riesgo cardiovascular aunque no lo hace con los de estrés oxidativo. La PCR, la MPO y el MDA se correlacionan positivamente con los triglicéridos. El MDA se correlaciona con el colesterol; la PCR con el Índice Aterogénico; el IMC y la circunferencia de cintura resultaron las variables que más influyen sobre la concentración de triglicéridos e Índice aterogénico. El MDA se correlaciona positivamente con la edad en individuos menores de 65 años. El consumo de frutas y verduras se asociaría negativamente al MDA en una regresión múltiple incluyendo solo individuos de 40 a 65 años. Los resultados de este estudio indican que las variables lipídicas son las que mejor se correlacionan con el estrés oxidativo. El IMC y la circunferencia de cintura se han comportado como las variables más influyentes sobre los valores de lipídicos. Los hábitos dietéticos relacionados con el consumo de frutas y verduras ayudan a disminuir la concentración de MDA que tiende a incrementarse con la edad en individuos de 40 a 65 años en nuestra población. / Oxidative stress and inflammation appear to play an important role in the process of ageing and in the associated dysfunction of the human cardiovascular system. Lifestyle habits such as smoking, alcohol consummation, physical exercises, might alter the redox state of body tissues and affect the relationship of oxidative stress markers with age. Information about the oxidative status of human populations is required to verify the role of oxidative damage in the ageing related changes of the cardiovascular system, and to identify what are the most influential cardiovascular risk factors on the oxidative damage associated to ageing and the influence of lifestyle in this relation. This study was conducted in a population of 160 healthy individuals or with mild disease treated and compensated, in an evenly distributed range of age of age 16 to 84 years. General biochemical, anthropometric data, personal, dietary supplements and determining the concentration of variables related to oxidative stress and / or cardiovascular risk: Myeloperoxidase (MPO), Homocysteine, ultrasensitive C-reactive protein (CRP) and Malondialdehyde (MDA) was collected of each patient. Information about individual lifestyle patterns were also collected. Interactions between variables were assessed by correlation (Pearson or Spearman) and multiple regression analyses. Results. There were not gender differences in the variables of oxidative stress and inflammation assessed in this study. hsCRP was significantly associated with age, Framingham index, waist circumference, body mass index, blood glucose and plasma triglycerides. MDA plasma concentration was related to the values of cholesterol and triglycerides blood levels. MPO was associated with the plasma concentration of triglycerides and the atherogenic index. BMI and waist circumference are variables with more influence in the concentration of triglycerides and atherogenic index. The MDA was positively correlated with age in individuals younger than 65 years. The consumption of fruits and vegetables were negatively associated with MDA in a multiple regression including only individuals from 40 to 65 years. These results indicate that plasma concentrations of triglycerides and total cholesterol positively associate with oxidative stress and inflammation in a general human population. In addition, due to the body mass index appears to be the most influential factor on the lipid plasma levels, it may be a good marker of this association. Eating habits associated with the consumption of fruits and vegetables help reduce the concentration of MDA, which tends to increase with age in individuals 40 to 65 years in our population.

Introducción: Las recomendaciones del ATPIII y las SSCC europeas en prevención primaria cardiovascular aconsejan para la estimación del riesgo individual las funciones de Framingham y SCORE respectivamente. Ambas disponen de versiones calibradas para la población española. Todas, excepto Framingham(ATPIII), han sido derivadas para aplicarlas en un rango de edad limitado. Por otra parte, ninguna de estas funciones predice el riesgo cardiovascular total, ya que SCORE y SCORE calibrada sólo estima el riesgo de muerte y Framingham(ATPIII) y REGICOR el riesgo coronario. Sin embargo todas las medidas preventivas van dirigidas a la prevención de la enfermedad cardiovascular globalmente y las funciones son utilizadas como proxi del riesgo cardiovascular total. El objetivo es determinar cuál de estas funciones de estimación del riesgo cardiovascular es más útil para seleccionar al mayor número de pacientes con incidencia total de episodios cardiovasculares elevada. Método: Estudio observacional de cohortes de 1642 pacientes de 20 a 79 años no diabéticos, sin enfermedad cardiovascular establecida, en una Unidad de Hipertensión y Riesgo Vascular, seguidos un tiempo mediano de 3,8 años (rango 1- 10 años). Se registraron todos los episodios cardiovasculares mayores incidentes. Se calculó el riesgo predicho individual utilizando cada función. Se analizó el grado de concordancia para clasificar en grupos de riesgo utilizando los puntos de corte ≥5% en SCORE y SCORE calibrada, >20% para Framingham(ATPIII) y ≥10% en REGICOR. Se estimó para cada función la sensibilidad, especificidad, CPP, CPN, Odds ratio diagnóstica y exactitud. Se estimó la densidad de incidencia por el método de Mantel-Haenzel, y la incidencia acumulada en grupos de riesgo obtenidos al aplicar los algoritmos y compararlos mediante análisis de Kaplan-Meier. Se compararon las curvas de supervivencia mediante test de Breslow. Resultados: SCORE calibrada clasificó de alto riesgo a un 13,5%, SCORE a un 9,8%, Framingham(ATPIII) al 8,8% y REGICOR a un 3,5%. Durante el seguimiento 74 pacientes presentaron un primer episodio cardiovascular. La concordancia a la hora de clasificar en grupos de riesgo entre Framingham y SCORE (Kappa=0,37), y entre SCORE calibrada y REGICOR (Kappa=0,34) fue débil. Para cada función, el grupo de alto riesgo presentó un HR superior a 4 respecto al grupo de riesgo moderado/bajo. Todas las funciones presentaron una baja sensibilidad sin diferencias significativas, así como una exactitud moderada para discriminar pacientes con episodio cardiovascular. Al comparar SCORE vs Framingham(ATPIII) y SCORE calibrada vs REGICOR, la incidencia de episodios cardiovasculares en los grupos con discordancia en la clasificación de alto riesgo no presentó diferencias significativas. SCORE excluyó un 4,8% de pacientes de alto riesgo frente a un 5,8% por Framingham(ATPIII). SCORE calibrada excluyó un 0,4% de pacientes de alto riesgo frente a un 10,3% en el caso de REGICOR. Además, SCORE calibrada seleccionó un 4,2% más de pacientes respecto a SCORE con una incidencia significativamente más elevada que el grupo de riesgo moderado/bajo. En las mujeres por falta de potencia estadística no se observaron diferencias significativas. En los hombres SCORE excluyó un 7,1% de pacientes de alto riesgo frente a un 10,6% por Framingham(ATPIII), mientras que SCORE calibrada excluyó un 0,4% de pacientes de alto riesgo frente a un 16,1% por REGICOR con una probabilidad acumulada de ECV a los 5 años del 19%. Además, SCORE calibrada incluyó un 5% más de pacientes que SCORE con una probabilidad acumulada de episodios cardiovasculares a los 5 años del 17%. Conclusión: En prevención primaria, aunque el rendimiento de las cuatro funciones analizadas no presenta diferencias significativas, la concordancia entre ellas es débil, siendo SCORE calibrada la más útil para seleccionar al mayor número de pacientes con una incidencia de episodios cardiovasculares aumentada. / Background: The recommendations of ATPIII and the European scientific societies in cardiovascular primary prevention advise the estimate of the individual risk by Framingham and SCORE functions respectively. Both have versions calibrated for the Spanish population. The objective is to determine which of these functions is more useful to select to the greater number of patients with high cardiovascular incidence. Method: Longitudinal study of 1642 non-diabetic patients, without previous history of cardiovascular disease attending to a Hypertension and Vascular clinic. High-risk patients were considered those with ≥5% risk according to SCORE and calibrated SCORE, >20% on Framingham(ATPIII) and ≥10% on REGICOR. Major cardiovascular events were collected during a 3 year median follow-up (range 1-10 años) and analysed by Kaplan-Meier. Results: 13,5% of patients was considered of high-risk with calibrated SCORE function, 9,8& with SCORE, 8,8% with Framingham(ATPIII) and 3,5% with REGICOR. The concordance between SCORE and Framingahm(ATPIII) (Kappa=0,37), and between calibrated SCORE and REGICOR (Kappa=0,34) was poor. During follow-up 74 cardiovascular events occurred. The incidence of cardiovascular events in groups with disagreement in high risk classification, did not present differences, upon compared SCORE vs Framingham(ATPIII) and calibrated SCORE vs REGICOR. SCORE excluded a 4,8% of high risk patients as compared to a 5,8% by Framingham(ATPIII). Calibrated SCORE excluded a 0,4% of high risk patients as compared to a 10,3% in the case of REGICOR. Furthermore, calibrated SCORE selected 4,2% patients more than SCORE with incidence of cardiovascular events significantly highest that moderate/low risk group. In women, by lack of statistics power, it’s not observed meaningful differences. In the men SCORE excluded 7,1% of high risk patients as compared to 10,6% by Framingham(ATPIII). Calibrated SCORE excluded 0,4% of high risk patients as compared to 16,1% by REGICOR with acumulative probability of cardiovascular events at 5 years of 19%. Furthermore, calibrated SCORE included a 5% of men more than SCORE with an acumulative probability of cardiovascular events at 5 years of 17%. Conclusions: In primary prevention, calibrated SCORE is the most useful to select the greater number of patients with a cardiovascular events incidence increased.

Accumulating evidence suggests that measures of abdominal obesity outperform BMI in predicting diabetes and cardiovascular risk. However, it is debated which measure of obesity should be used. Currently, waist circumference (WC) is most commonly used and codefines the metabolic syndrome.

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.

<p>Diss. (sammanfattning) Umeå : Umeå universitet, 2003</p> / digitalisering@umu

With the severity of cardiovascular disease (CVD) and the related mortality rate to this disease, new methods are necessary for risk assessment and treatment prior to the onset of the disease. The current paradigm in CVD risk assessment has shifted towards the multivariate approach over the individual use of traditional risk factors or lipid measurements. Through a combination of analytical techniques and multivariate statistical analysis, a novel method of cardiovascular risk assessment was developed. The analytical techniques employed include density gradient ultracentrifugation (DGU) and matrix assisted laser desorption ionization mass spectrometry (MALDI-MS) applied to human serum. These techniques provided detailed information about the characterization of the lipoproteins and their structural components, specifically the apolipoproteins belonging to high density lipoproteins (HDL). This information when combined with multivariate statistical analysis provided a method that accurately identified the presence of CVD in clinical studies between cohorts of subjects that had been previously diagnosed with CVD and cohorts of subjects that had been identified as healthy controls (CTRL) based on a clear angiography. The lipoprotein density profiles were divided into subclasses based on their density and measured using a fluorescent probe to tag the lipoprotein particles. Use of multiple ethylenediaminetetraacetic acid (EDTA) based solutes allowed for the manipulation of the density gradient formation in order to separate the lipoproteins by specific density ranges in order to achieve better baseline separation of the profiles. Application of the integrated fluorescence intensities for each subclass of lipoprotein to linear discriminant analysis/sliced inverse regression (LDA/SIR) and quadratic discriminant analysis (QDA) yielded an advanced and accurate form of risk assessment for CVD. This method was found to be highly accurate as well as identify potential atherogenic lipoprotein subclasses through studying the LDA/SIR prediction equation generated. It was also shown that the LDA/SIR equation could be used to monitor medical treatment and lifestyle change for their effects on the risk assessment model. Further study into the atherogenicity of HDL through analysis of the apolipoproteins using MALDI-MS led to identification of potential risk factors that could be added to the statistical analyses. These risk factors included mass differences in the Apolipoprotein A-I (Apo A-I) and Apolipoprotein C-I (Apo C-I) between CVD and CTRL samples as well as the presence of specific mass peaks related to Apolipoprotein A-II (Apo A-II) that were primarily found in the CVD samples. These differences, in addition to the lipoprotein density profile data, were found to increase the potential accuracy of CVD risk assessment. The combination of these methods has shown great potential in the assessment of CVD risk as well as the ability to increase researchers' understanding of the nature of VD and how to treat it.