Le vieillissement vasculaire est un phénomène inéluctable. Il s'accompagne de modifications structurelles et fonctionnelles du système cardio-vasculaire constituant la rigidité vasculaire. Ce processus dégénératif affecte essentiellement la matrice extra cellulaire des artères élastiques. La perte de l'élasticité du système vasculaire va impacter la fonction ventriculaire gauche et la perfusion cardiaque, rénale et cérébrale par des mécanismes différents. La rigidité vasculaire est un puissant marqueur de risque cardio-vasculaire. Cette notion est peu répandue dans le domaine de la cardiologie interventionnelle alors qu'elle pourrait avoir des implications pronostiques et thérapeutiques importantes. Nous nous sommes intéressés à deux domaines de la cardiologie interventionnelle, pour lesquels la rigidité vasculaire pourrait ouvrir de nouvelles voies de recherche, la maladie coronaire et le traitement interventionnel du rétrécissement aortique. Concernant la maladie coronaire il existe un besoin de mieux comprendre la physiopathologie de la microcirculation et de l'ischémie myocardique. La survenue des accidents coronaires aigus reste également incomplètement comprise. Nous avons abordé la problématique par une approche épidémiologique en étudiant l'impact pronostique de la rigidité vasculaire sur la mortalité liée aux coronaropathies dans une cohorte de 1034 patients hypertendus avec 30 années de suivi. La rigidité vasculaire a été appréciée par la pression pulsée et un score d'athérosclérose de l'aorte abdominale. Un lien très fort a été mis en évidence entre la rigidité vasculaire et la survenue d'infarctus du myocarde. Nous avons ensuite développé un moyen d'étudier la rigidité vasculaire localement au niveau des artères coronaires. Nous avons mis au point une technique de mesure de la vitesse de l'onde de pouls coronaire. Cette technique repose sur l'utilisation d'un guide de pression ntra-coronaire et un algorithme breveté du traitement de signal. Nous sommes parvenus à mesurer une vitesse de l'onde de pouls sur 71 artères coronaires chez 49 patients. Nous avons observé une vitesse de l'onde de pouls plus lente témoignant d'artères plus compliantes chez les patients présentant un infarctus du myocarde en comparaison aux patients présentant un angor stable. Nous avons également constaté une augmentation de la vitesse de l'onde de pouls après implantation d'un stent endocoronaire témoignant d'une rigidification attendue de l'artère coronaire. Ces travaux pourraient ouvrir une nouvelle voie de recherche dans la compréhension de l'ischémie myocardique et de la survenue de l'accident coronaire aigu à savoir l'interaction rigidité vasculaire globale et rigidité locale coronaire. Concernant le traitement interventionnel du rétrécissement aortique, de nouveaux facteurs prédictifs du bénéfice de l'intervention sont nécessaires chez des patients souvent âgés et fragiles. Nous nous sommes intéressés à l'étude du volume de calcifications de l'aorte, reflet de la rigidité vasculaire. Ce paramètre a été mesuré par scanner chez des patients traités par remplacement valvulaire aortique par voie percutanée appelé TAVI pour transcatheter aortic valve implantation. Nous avons d'abord montré que le volume de calcifications de l'aorte ascendante était un puissant marqueur de risque indépendant de mortalité cardiaque et d'insuffisance cardiaque sur une série de 127 patients consécutifs traités par TAVI, avec un suivi médian de 907 jours. Ce travail a ensuite été complété en étudiant le volume de calcifications de l'aorte totale sur une série de 164 patients. Le volume de calcifications de l'aorte complète était prédicteur de mortalité totale et cardiaque. De plus, chaque segment d'aorte pris séparément (aorte ascendante, descendante et abdominale) prédisait la mortalité cardiaque. Enfin, seul le volume de calcifications du segment ascendant était prédicteur d'insuffisance cardiaque [etc…] / Vascular aging is an inevitable phenomenon. It is accompanied by structural and functional modifications of the cardiovascular system mainly referred to as vascular stiffening. This degenerative process essentially affects the extracellular matrix of the elastic arteries. The loss of elasticity of the vascular tree affects left ventricular function as well as cardiac, renal and cerebral perfusions involving different mechanisms. Vascular stiffness is a powerful risk marker of cardiovascular disease. However, most interventional cardiologists are not familiar with this concept while it may have both important prognostic and therapeutic implications. We tackled two areas of interventional cardiology, where vascular stiffness may open new fields of research; coronary artery disease and interventional treatment of aortic stenosis namely, transcatheter aortic valve implantation (TAVI). With regards to coronary artery disease there is a need to better understand the pathophysiology of microcirculation and myocardial ischemia. Moreover, the occurrence of acute coronary events is also incompletely understood. Our first approach was epidemiological. We studied the prognostic impact of vascular stiffness on coronary artery disease mortality in a cohort of 1034 hypertensive patients after 30 years of follow-up. Vascular stiffness was assessed both by pulse pressure and by a score related to atherosclerosis of the abdominal aorta. A strong link was found between vascular stiffness and the occurrence of myocardial infarction and coronary artery disease related deaths. We then developed a way to study the local vascular stiffness at coronary artery level by measuring coronary pulse wave velocity. This technique relies on the use of an intracoronary pressure wire and a patented signal processing algorithm. We measured a coronary pulse wave velocity on 71 coronary arteries in 49 patients. Interestingly, patients with acute coronary syndromes had a lower coronary pulse wave velocity (which means more compliant arteries) when compared to patients with stable coronary artery disease. After an endocoronary stent implantation we noticed an increase of coronary pulse wave velocity in line with an expected stiffening. This work opens a new avenue of research regarding coronary perfusion physiology and plaque complications by studying the interaction of regional vascular stiffness and local coronary stiffness. Regarding TAVI, a procedure that often concerns elderly and frail patients, new factors predicting the benefit of the intervention are needed. We studied aortic calcifications as a surrogate of vascular stiffness. This parameter was measured by CT scan before TAVI. We first showed in 127 consecutive patients with a median follow-up of 907 days that ascending aorta calcifications were a powerful risk marker of cardiac mortality and heart failure after TAVI. This study was then completed by studying the volume of the whole aorta in 164 patients. The volume of calcifications of the whole aorta was a predictor of both all-cause and cardiac mortality. In addition, each segment of aorta taken separately (ascending, descending and abdominal aorta) predicted cardiac mortality. Finally, only ascending aorta calcifications predicted heart failure. These results support the hypothesis that ascending aorta calcifications are a marker of vascular stiffness and contribute to the left ventricular afterload. Moreover the volume of the whole aorta could mirror the global atherosclerosis burden of the patient. This easily measurable parameter could thus represent a new risk stratification tool in patients treated with TAVI. This work on vascular stiffness opens a new field of research in several areas of interventional cardiology. Regarding coronary artery disease, coronary pulse wave velocity could represent a way to better understand coronary perfusion, microcirculation, ischemia and the occurrence of coronary plaque rupture [etc...]

Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro / O diabetes mellitus(DM) e as disfunções tireoidianas(DT) são as duas desordens endocrinológicas mais comuns na prática clínica. A DT não reconhecida pode interferir no controle metabólico e adicionar mais risco a um cenário predisponente à doença cardiovascular. O objetivo deste estudo foi avaliar a prevalência da DT em pacientes com diabetes mellitus tipo 1 e tipo 2 (DM1 e DM2) e avaliar o risco cardiovascular em pacientes com DM2 com e sem DT utilizando parâmetros clínicos e laboratoriais. Trata-se de um estudo observacional de corte transversal. Foram avaliados 304 pacientes com DM2 e 82 pacientes com DM1. Os pacientes foram submetidos a um inquérito clínico-demográfico e avaliação laboratorial para determinação do perfil lipídico, glicídico e da função tireoidiana. Os pacientes com DM2 tiveram seus escores de risco cardiovascular em 10 anos determinados pelas equações de Framingham e do UKPDS risk engine. A frequência de disfunção tireoidiana entre os 386 pacientes foi de 14,7%, sendo de 13% nos que não possuíam disfunção prévia. A disfunção mais frequente encontrada foi de hipotireoidismo subclínico, com 13% no DM1 e de 12% no DM2. A prevalência de anticorpos anti-tireoperoxidase (TPO) positivos foi de 10,8%, sendo de14,6% em pacientes com DM1.Foram diagnosticados 44 (11,2%) novos casos de disfunção tireoidiana em pacientes que negavam ou desconheciam terem DT prévia.Destes novos casos, 12,8% em DM1 e 13,1% em DM2.Dos 49 pacientes com DT prévia, 50% dos DM1e 76% dos DM2 estavam compensados. Não foi observada diferença entre as médias do escore de risco de Framingham entre os pacientes DM2 com eutireoidismo e com hipotireoidismo subclínico. Observou-se uma associação entre o hipotireoidismo subclínico e risco cardiovascular nos pacientes com DM2 demonstrado pela diferença estatisticamente significativa entre as médias do escore UKPDS para doença coronariana não-fatal e fatal, acidente vascular cerebral fatal entre os dois grupos (p=0,007; 0,005;0,027 respectivamente). As demais funções tireodianas (hipotireoidismo clínico, hipertireoidismo clínico e subclínico) encontradas não foram analisadas devido ao pequeno número de pacientes em cada grupo.Concluímos que o rastreio da doença tireoidiana entre os pacientes com diabetes mellitus deve ser realizado rotineiramente considerando-se a prevalência de novos casos de DT diagnosticados e o fato de que os pacientes com DM2 e com hipotireoidismo subclínico avaliados possuírem um risco cardiovascular maior. Todavia, concluímos que estudos prospectivos e com maior número de pacientes são necessários para o esclarecimento do impacto da doença tireoidiana no risco cardiovascular do paciente com DM. / Diabetes mellitus and thyroid dysfunction (TD) are the two most common endocrine disorders in clinical practice. The unrecognized TD may adversely affect the metabolic control and add more risk to an already predisposing scenario for cardiovascular diseases. The objective of this study was to evaluate the prevalence of TD in patients with type 1 and type 2 diabetes mellitus (T1DM and T2DM) and to evaluate the cardiovascular risk of patients with T2DM with and without thyroid dysfunction using clinical and laboratory parameters. This is an observational cross-sectional study. We evaluated 304 patients with T2DM and 82 patients with T1DM. The patients underwent a clinical-demographic survey and laboratory evaluation to determine the lipid and glycemic profile and thyroid function. Patients with T2DM had their 10 years cardiovascular risk scores determined by Framingham equations and the UKPDS risk engine. The frequency of TD among the 386 patients was 14.7% and 13% who denied previous TD. The most frequently TD was subclinical hypothyroidism, in 13% of patients with T1DM and in 12% of patients with T2DM.The prevalence of anti-TPO antibodies was 10.8%, being more frequently among patients with T1DM (14.6%). Forty-four (11.2%) new cases of TD were diagnosed during the study in patients who denied or were unaware of this clinical condition. Of the 49 patients with prior TD,50% of the T1DM and 76% of T2DM were compensated. No differencies were observed between the mean scores of the Framingham risk among patients with T2DM who had normal thyroid function compared to those with subclinical hypothyroidism. An association between subclinical hypothyroidism and cardiovascular risk in T2DM patients was found by statistically significant difference between the mean UKPDS scores for non-fatal and fatal CHD and fatal stroke between the two groups (p = 0,007;0,005;0027; respectively). The other TD (clinical hypothyroidism, clinical and subclinical hyperthyroidism) found were not analyzed due to the small number of patients in each group.We conclude that screening for thyroid disease among patients with diabetes mellitus should be routinely performed considering the prevalence of new cases diagnosed and the fact that patients with DM2 and subclinical hypothyroidism evaluated had a higher cardiovascular risk. However, prospective studies and with more patients are warranted to determine the impact of thyroid dysfunction in the cardiovascular risk of patients with diabetes.

Submitted by Simone Souza (simonecgsouza@hotmail.com) on 2018-05-23T16:26:16Z No. of bitstreams: 1 DISS_2011_ Fábio Liberali Weissheimer.pdf: 1640556 bytes, checksum: e2f968f9fd0f610356f2cea91b142b03 (MD5) / Approved for entry into archive by Jordan (jordanbiblio@gmail.com) on 2018-05-24T17:17:32Z (GMT) No. of bitstreams: 1 DISS_2011_ Fábio Liberali Weissheimer.pdf: 1640556 bytes, checksum: e2f968f9fd0f610356f2cea91b142b03 (MD5) / Made available in DSpace on 2018-05-24T17:17:32Z (GMT). No. of bitstreams: 1 DISS_2011_ Fábio Liberali Weissheimer.pdf: 1640556 bytes, checksum: e2f968f9fd0f610356f2cea91b142b03 (MD5) Previous issue date: 2011-09-05 / A hipertensão arterial sistêmica (HA) é uma condição sistêmica que envolve alterações estruturais das artérias e do miocárdio, gerando níveis de pressão arterial (PA) sustentadamente elevados. De causalidade multifatorial é grande problema de saúde devido às altas prevalência, morbidade, mortalidade e custos. Estudos brasileiros sobre incidência de HA são raros. Estudo feito em 2008 em Porto Alegre-RS pontuou que 80% dos pré-hipertensos, entre 40 e 50 anos, terão HA em 10 anos. Desta forma, torna-se pertinente estudar a incidência da HA em Cuiabá-MT para que se obtenham informações técnico-científicas que subsidiem políticas de combate a HA. Objetivo: Analisar a incidência de HA e fatores associados em préhipertensos em Cuiabá-MT. Método: Coorte prospectivo de base populacional aprovado pela CEP/HUJM com acompanhamento em 6,8 anos de população fonte de 400 pré-hipertensos entre 2003 e 2010. Foram usadas estatísticas descritivas e inferenciais, risco relativo (IC 95%), teste de qui-quadrado de Pearson, p<0,05 e regressão múltipla de Poisson robusta. Resultados: População amostral de 171 indivíduos, 61,9% homens e 38,1% mulheres, idade média de 46,6 anos. Tempo de follow up de 6,8 anos. Média de anos de estudo de 9,5 anos. Renda média per capita de R$ 902,20. Foi observado no estudo que: 10,5% dos entrevistados admitiram consumir sal em excesso; 76,6% tomam café diariamente; 26,9% são sedentários; 13,4% fumam cigarros diariamente e 28,6% são obesos. A incidência de HA geral foi de 58,5% sendo que 86% destes estavam com PA descontrolada. Estratificando por exposição, a incidência de HA encontrada foi de 63,8% em indivíduos com renda per capita menor que 2 salários mínimos; 65,7% em indivíduos que consomem café diariamente; 71,7% nos sedentários e 77,6% nos obesos. Após regressão, mantiveram associadas ao desfecho HA às exposições (fatores de risco): obesos (p<0,001), tempo de assistir à televisão maior a 4 horas (p< 0,000), consumo de café diário (p< 0,005), renda menor que 2 salários mínimos (p< 0,041), número de moradores maior que 4 (p<0,047) e idade maior que 60 anos (p<0,000). Conclusão: O estudo demonstrou que há risco de 86% de um pré-hipertenso residente na área urbana de Cuiabá-MT desenvolver HA em 10 anos, e que a mesma está associada a fatores de risco conhecidos, em sua maioria modificáveis. Algumas associações sugerem maior estudo. Adoção de políticas de prevenção, tratamento e controle desta moléstia são necessárias. / The systemic arterial hypertension is a systemic condition which involves structural alterations of the artery and of the myocardium, generating continuously high levels of blood pressure. Of multifactorial causality, it is a great health issue due to its high prevalence, morbidity, mortality and costs. Brazilian researches on systemic arterial hypertension incidence are unusual. Research conducted in 2008 in Porto Alegre (RS) stated that 80% of the pre-hypertensive patients between 40 and 50 years will have systemic arterial hypertension in 10 years. Therefore, it is relevant to study the incidence of systemic arterial hypertension in Cuiabá (MT) in order to obtain technical-scientific information that subsidizes prevention policies against systemic arterial hypertension. Objective: To analyze the incidence of systemic arterial hypertension and associated factors on prehypertensive patients in Cuiabá (MT). Methods: Population-based prospective cohort approved by CEP/HUJM, with population of 400 pre-hypertensive patients watched for 6,8 years, from 2003 through 2010. Descriptive and inferential statistics were used, relative risk (Confidence Intervals - CI 95%), Pearson’s chi-square test, p<0,05 and multiple Poisson regression with robust variance. Results: Population sample of 171 patients, 61,9% men and 38,1% women, average of 46,6 years old. Follow-up time of 6,8 years. Schooling time of 9,5 years. Average per capita income of R$ 902,20. It was observed in this research that: 10,5% admit high level of salt consumption; 76,6% have daily coffee consumption; 26,9% are sedentary; 13,4% smoke cigarrettes; and 28,6% are obese. General systemic arterial hypertension incidence totaled 58,5%, from which 86% presented uncontrolled blood pressure. Stratified by exposition, the incidence of systemic arterial hypertension found was 63,8% in patients with per capita income below 2 minimum wages; 65,7% in patients that consume coffee daily; 71,7% in sedentary patients; and 77,6% in the obese. After regression, the following expositions remained associated (risk factors): obese (p<0,001), time spent watching TV higher than 4h (p< 0,000), daily coffee consumption (p< 0,005), income lower than 2 minimum wages (p< 0,041), number of inhabitants higher than 4 (p< 0,047) and age higher than 60 years old (p< 0,000). Conclusion: The research has shown that there is an 86% risk for a patient who is a resident of the urban area of Cuiabá (MT) to develop arterial hypertension in ten years, and this is associated to well known risk factors that are, in majority, modifiable. Some associations might demand a greater study. The adoption of prevention policies, treatment and control of this disease are required.

Os profissionais da área da saúde que atuam no serviço de atendimento pré-hospitalar podem estar sujeitos a fatores de risco cardiovasculares em razão do estilo de vida adotado e das características do trabalho. O objetivo principal do estudo foi avaliar a influência do plantão de 24 horas sobre a pressão arterial e os fatores de risco para afecções cardiovasculares nesses profissionais. Casuística e Método: Estudo transversal com 154 profissionais (90 enfermeiros, 41 médicos, 23 auxiliares de enfermagem) que atuavam no serviço de atendimento pré-hospitalar: Grupo de Atendimento Médico de Urgência (GRAU-193), Serviço Móvel de Urgência (SAMU-192) e Samu-Vale do Ribeira. Realizou-se medida da pressão arterial casual com aparelho automático validado e considerou-se hipertenso pressão 140/90mmHg e/ou uso de anti-hipertensivos. Procedeu-se a Monitorização Ambulatorial da Pressão Arterial (MAPA), durante o plantão no pré-hospitalar e em dia usual de atividade. Foram analisados o índice de massa corpórea (IMC), a circunferência abdominal (CA), a glicemia, o perfil lipídico e a proteína C reativa. O risco cardiovascular foi calculado pelo Escore de Risco de Framingham (ERF) e avaliada a presença da Síndrome Metabólica. Foram utilizados os instrumentos: Índice de Qualidade de Sono de Pittsburg, Self Report Questionnaire, Inventário de Depressão de Beck, Escala de Estresse no Trabalho e Malasch Burnout Inventory. O nível de significância adotado foi p<0,05, utilizou-se análise univariada e regressão logística para as variáveis significativas. Resultados: As características dos participantes foram: idade 40,9±7,8 anos. Sedentarismo 64,9%, CA alterado 70,2% e IMC sobrepeso/obeso de 65,6%. Alteração de glicose em 11%, colesterol elevado em 11%, LDL-c alto 7,8%, HDL-c alto 11% e triglicérides em 16,2%, proteína C reativa 40,3% nos quartis mais altos. A prevalência da hipertensão arterial pela medida casual no pré-hospitalar foi 33,1% e em dia usual de atividade 13,6%. Na MAPA de 24h no pré-hospitalar 29,3%, dia usual de atividade 22,6%; MAPA da vigília no pré-hospitalar 26,6%, dia usual de atividade 18,5%; MAPA no sono pré-hospitalar 63,0%, dia usual de atividade 42,5%. Houve diferenças significativas nos níveis pressóricos pré-hospitalares em relação ao dia usual de atividade para medida casual sistólica e diastólica (124,9±15,1mmHg/79,0±10,8 mmHg vs. 122,1±14,5mmHg/76,7±10,5mmHg) e na MAPA no período de sono, para a pressão diastólica (110,5±11,5mmHg/72,6±9,5mmHg vs. 111,8±10,8mmHg/67,6±7,9 mmHg). Os fatores associados à hipertensão foram a pela medida casual: HDL-c > 40 mg/dL (Odds Ratio (OR) 0,257; intervalo de confiança (IC) 95%: 0,0810,813) e ERF > 10% (OD: 23,159; IC 95%: 2,029264,378). b) pela MAPA: no período de 24 horas: sexo masculino (OR: 2,717; IC 95%: 1,206-6,122); trabalhar cansado raramente/nunca (OR: 0,197; IC 95%: 0,061-0,638) e às vezes (OR: 0,174; IC 95%: 0,050-0,614); glicemia > 100 mg/dL (OR: 9,983; IC 95%: 1,560-63,881). Para MAPA da vigília: sexo masculino (OR: 3,245; IC 95%: 1,385-7,606); trabalhar cansado raramente/nunca (OR: 0,142; IC 95%: 0,042-0,481); e às vezes (OR: 0,163; IC 95%: 0,045-0,590); glicemia > 100 mg/dL (OR:11,1809; IC 95%: 1,632-76,60) e IMC > 25kg/m2 (OR: 1,101; IC 95%: 1,006-1,206). Para MAPA do sono: IMC > 25kg/m2 (OR: 1,119; IC 95%: 1,021-1,226) e presença de sono diurno (OR: 0,140; IC 95%: 0,065-0,300). O Escore de Risco de Framingham foi médio/alto em 10,6%; Síndrome Metabólica presente em 28,6%, má qualidade de sono em 41,6%, transtornos mentais comuns em 16,2%, depressão em 7,8%, média de estresse no trabalho em 50,1% e Burnout em 29%. Conclusão: houve diferenças pressóricas durante o plantão no serviço pré-hospitalar em relação a um dia usual de atividade, e os profissionais estudados estavam expostos a fatores de risco modificáveis, sendo necessárias mudanças no estilo de vida / Professionals that work in pre-hospital assistance might be subject to the cardiovascular risk factors due to their adopted lifestyle and specific characteristics of their occupation. Casuistic and Method: Transversal study with 154 professionals (90 nurses, 41 physicians, 23 nurse auxiliaries) that work in prehospital: Grupo de Atendimento Médico de Urgência [Group of Emergency Medical Assistance] (GRAU-193), Serviço Móvel de Urgência [Emergency Rescue Service] (SAMU-192) and Samu-Vale do Ribeira. Measures were performed regarding casual blood pressure; it was considered arterial hypertensive pressure (HA) 140/90mmHg and/or use of antihypertensives. The Ambulatorial Monitoring of Blood Pressure (ABPM) was performed during the duty on prehospital and also on casual day of activities. The Body Mass Index (IMC), Abdominal Circumference (CA), glucose, lipids profile and C-reactive protein were analyzed. The cardiovascular risk was used Framingham Risk Score (ERF), Metabolic Syndrome were analyzed. The used tools were: Pittsburg Sleep Quality Index, Self Report Questionnaire, Beck Depression Inventory, Job Stress Scale and Malasch Burnout Inventory. Data were processed on SPSS System v.7.5. The level of significance adopted was p <0,05, univariate analysis was used and the logistic regression was performed for remarkable variables. Results: Age of 40,9 ± 7,8 years. Sedentary lifestyle 64,9%, CA altered 70,2% and IMC overweight/obese of 65,6%. Glucose alteration in 11%, elevated cholesterol in 11%, high LDL-c in 7,8%, high HDL-c in 11% and triglycerides in 16,2%, C-reactive protein in 40,3% on higher quartiles. The prevalence of prehospital HA: 33,1% and casual day of activities 13,6%. ABPM: 24h prehospital 29,3%, casual day of activities 22,6%; ABPM: daytime prehospital 26,6%, casual day of activities 18,5%; ABPM: nighttime prehospital 63,0%, casual day of activities 42,5%. There were significant differences on pressoric levels of prehospital in comparison with casual day of activities for casual measure of systolic and diastolic pressures (124,9±15,1 mmHg/79,0±10,8 mmHg vs. 122,1±14,5 mmHg; /76,7±10,5mmHg), and on ABPM of nighttime period for diastolic pressure (110,5 ± 11,5 mmHg/72,6±9,5 mmHg vs. 111,8±10,8 mmHg/67,6±7,9 mmHg). Factors related with casual HA: HDL-c > 40 mg/dL (Odds Ratio (OR) 0,257; confidence interval (IC) 95%: 0,0810,813) and ERF >10% (OD: 23,159; IC 95%: 2,029264,378). The HA measured by ABPM: on 24 hours period: male gender (OR: 2,717; IC 95%: 1,206-6,122); never/occasionally work tired (OR: 0,197; IC 95%: 0,061-0,638) and sometimes (OR: 0,174; IC 95%: 0,050-0,614); glucose > 100mg/dL (OR: 9,983; IC 95%: 1,560-63,881). For daytime: male gender (OR: 3,245; IC 95%: 1,385-7,606); never/occasionally work tired (OR: 0,142; IC 95%: 0,042-0,481); and sometimes (OR: 0,163; IC 95%: 0,045-0,590); glucose > 100mg/dL (OR: 11,1809; IC 95%: 1,632-76,60) and IMC > 25kg/m2 (OR: 1,101; IC 95%: 1,006-1,206). For nighttime period: IMC > 25kg/m2 (OR: 1,119; IC 95%: 1,021-1,226) and presence of somnolence during day (OR: 0,140; IC 95%: 0,065-0,300). Prevalence of Metabolic Syndrome: 28,6%; Framingham Risk Score: medium/high: 10,6%; poor quality of sleeping 41,6%, common mental disorders: 16,2%, depression: 7,8%, average job stress: 50,1% and Burnout 29%. It might be concluded: that there were pressoric differences during duty on prehospital in comparison with a casual day of activities, and that these professionals are exposed to the modifiable risk factor and need changes in their lifestyles.

<p>Inflammation and oxidative stress may be involved in atherogenesis. This thesis describes clinical studies of prostaglandin F_2α (PGF_2α), an inflammatory mediator, and the isoprostane 8-iso-PGF_2α, a reliable indicator of oxidative stress, and cytokine-related inflammatory mediators and indicators in healthy subjects and in a population-based cohort of Swedish men. </p><p>PGF_2α and 8-iso-PGF_2α formation in healthy subjects varied considerably between days with a mean intra-individual coefficient of variation of 41 % and 42 %, respectively. A morning urine sample reflected the basal level of 8-iso-PGF_2α formation as accurately as a 24-hour urine collection, and represents a more practical alternative to the 24-hour urine collection in clinical studies. PGF_2α formation (as measured by urinary 15-keto-dihydro-PGF_2α) was increased in patients with type 2 diabetes and in smokers independent of other cardiovascular risk factors. These results indicated an on-going cyclooxygenase (COX)-mediated inflammatory reaction related to these conditions. Further, an increased formation of isoprostanes (as measured by urinary 8-iso-PGF_2α) was found in patients with type 2 diabetes and in smokers, indicating a high level of oxidative stress in these men. The smokers had also increased levels of the cytokine interleukin-6, indicating an on-going cytokine-related inflammatory reaction. The inflammatory indicators C-reactive protein and serum amyloid A were related to overweight but not independently associated to type 2 diabetes. High levels of serum selenium in middle-aged men predicted reduced formation of PGF_2α and 8-iso-PGF_2α 27 years later.</p><p>In summary, low-grade, chronic COX-mediated and possibly cytokine-related inflammation, and oxidative stress, seem to be joint features of type 2 diabetes and smoking, two major risk factors of atherosclerosis, in elderly men. Inflammation and oxidative stress may represent a possible common pathogenetic link between established risk factors for atherosclerosis and atherogenesis.</p>

Inflammation and oxidative stress may be involved in atherogenesis. This thesis describes clinical studies of prostaglandin F2α (PGF2α), an inflammatory mediator, and the isoprostane 8-iso-PGF2α, a reliable indicator of oxidative stress, and cytokine-related inflammatory mediators and indicators in healthy subjects and in a population-based cohort of Swedish men. PGF2α and 8-iso-PGF2α formation in healthy subjects varied considerably between days with a mean intra-individual coefficient of variation of 41 % and 42 %, respectively. A morning urine sample reflected the basal level of 8-iso-PGF2α formation as accurately as a 24-hour urine collection, and represents a more practical alternative to the 24-hour urine collection in clinical studies. PGF2α formation (as measured by urinary 15-keto-dihydro-PGF2α) was increased in patients with type 2 diabetes and in smokers independent of other cardiovascular risk factors. These results indicated an on-going cyclooxygenase (COX)-mediated inflammatory reaction related to these conditions. Further, an increased formation of isoprostanes (as measured by urinary 8-iso-PGF2α) was found in patients with type 2 diabetes and in smokers, indicating a high level of oxidative stress in these men. The smokers had also increased levels of the cytokine interleukin-6, indicating an on-going cytokine-related inflammatory reaction. The inflammatory indicators C-reactive protein and serum amyloid A were related to overweight but not independently associated to type 2 diabetes. High levels of serum selenium in middle-aged men predicted reduced formation of PGF2α and 8-iso-PGF2α 27 years later. In summary, low-grade, chronic COX-mediated and possibly cytokine-related inflammation, and oxidative stress, seem to be joint features of type 2 diabetes and smoking, two major risk factors of atherosclerosis, in elderly men. Inflammation and oxidative stress may represent a possible common pathogenetic link between established risk factors for atherosclerosis and atherogenesis.

Šiame darbe apžvelgėme Vilniaus Universiteto Širdies ir kraujagyslių ligų klinikos Prevencinės kardiologijos poskyryje nuo įkūrimo sukauptą patirtį (1997-2008). Apibendrinome tyrimų rezultatus 1624 pacientams, sergantiems koronarine širdies liga, 977 įvairios kardiovaskulinės rizikos asmenims (sergantiems metaboliniu sindromu, cukriniu diabetu, dislipidemija, arterine hipertenzija, sveikiems kontroliniams), genetiniame projekte ištyrėme 67 šeimų 236 asmenis. Gyvensenos, rizikos veiksnių ir kardioprotekcinių vaistų vartojimo tyrimas koronarine širdies liga sergantiems pacientams 22 Europos šalyse išryškino esminius Lietuvos ir kitų šalių pacientų priežiūros skirtumus. Nustatėme, kad dauguma Lietuvos pacientų nepasiekia kardiovaskulinės prevencijos tikslų, ypač gydant dislipidemijas. Tyrimas leido daryti išvadą, kad Lietuvoje būtina ženkliai pakelti kardiovaskulinės prevencijos lygį. Tyrėme tradicinių rizikos veiksnių paplitimą tarp pacientų, sergančių koronarine širdies liga, ir parodėme, kad šie rizikos veiksniai dažnesni, nei nurodoma literatūroje. Mūsų duomenimis net 98% koronarinių pacientų turi bent vieną iš keturių tradicinių rizikos veiksnių. Du trečdaliai (66,5%) koronarine širdies liga sergančių jaunesnių pacientų (<55 metų) turėjo du ir daugiau rizikos veiksnius. Nustatėme statistiškai reikšmingą ryšį tarp aterosklerozės progresavimo vainikinėse arterijose ir kai kurių rizikos veiksnių: padidėjusio kraujospūdžio, gliukozės, homocisteino, lipoproteino (a), mažo... [toliau žr. visą tekstą] / This paper reviews the 1997−2008 experience gained by the Preventive Cardiology unit since its establishment in the department of Cardiovascular diseases of Vilnius University. We summarize the results of managing 1624 patients with coronary heart disease, 977 subjects with different cardiovascular risk (metabolic syndrome, diabetes, dyslipidaemia, arterial hypertension, healthy controls), evaluated 236 subjects from 67 families in the genetic project. A survey on the lifestyle, risk factors and use of cardioprotective drug therapies in patients with coronary heart disease from 22 European countries has showed major patient management differencies between Lithuania and other countries. The large proportion of patients in Lithuania do not achieve the targets for cardiovascular disease prevention, especially in lipid management. There is still considerable potential in Lithuania to raise standarts of cardiovascular prevention. We analyzed the prevalence of conventional risk factors among our patients with coronary heart disease and showed that they are more common than described in the literature. Our data revealed that 98% of coronary patients had at least one of four conventional risk factors. Two-thirds (66,5%) of younger patients (<55 years) with coronary heart disease had two and more risk factors. We have found statistically significant correlation between atherosclerosis progression rate in the coronary arteries and risk factors: elevated blood pressure, blood... [to full text]

L’étude visait à décrire la transition nutritionnelle et ses liens avec des facteurs de risque de maladies cardiovasculaires (MCV) dans une ville secondaire du Bénin et dans ses environs ruraux, puis de comparer à cet égard, les habitants de la petite ville avec ceux du milieu rural et de la métropole. Les sujets de 25 à 60 ans (n = 541), apparemment en bonne santé, ont été aléatoirement sélectionnés dans la petite ville de Ouidah (n = 171), sa périphérie rurale (n = 170) et dans la métropole Cotonou (n = 200). Les apports alimentaires et l’activité physique ont été cernés par trois rappels de 24 heures. Les données socioéconomiques ont été recueillies par questionnaire. La qualité de l’alimentation a été évaluée par un score de diversité alimentaire, un score d’adéquation en micronutriments et un score de prévention contre les maladies chroniques. Des mesures anthropométriques et de composition corporelle ont été prises. La tension artérielle a été mesurée. Des échantillons sanguins ont été prélevés pour déterminer le profil lipidique à l’aide du sérum et la glycémie à jeun plasmatique. La transition alimentaire était plus poussée dans la métropole que dans la petite ville et le milieu rural, et elle était marquée par des apports plus importants en viande, produits laitiers, œufs, légumes et huiles, mais plus faibles en céréales, poisson, légumineuses, fruits et fibres. La diversité alimentaire y était plus élevée, mais l’adéquation en micronutriments et la prévention étaient plus faibles que dans les autres sites. Il n’y avait pas de différences majeures entre le milieu rural et la petite ville pour la consommation et la qualité alimentaire. L’influence du niveau socioéconomique sur l’alimentation et sa qualité était surtout marquée dans la métropole. Un gradient positif du milieu rural vers la petite ville et la métropole a été observé pour l’obésité générale (8,8%; 12,3%; 18%, p = 0,031) et abdominale (28,2%, 41,5%, 52,5%; P<0,001) et pour le syndrome métabolique (4,1% ; 6,4% ; 11%; P = 0,035) d’après les critères de la Fédération Internationale de Diabète. La fréquence de tension artérielle élevée [TAE] (24,1% ; 21,6% et 26,5%, respectivement pour le milieu rural, la petite ville et la métropole), bien qu’importante, n’était pas significativement différente selon les sites. Le HDL-cholestérol bas était moins fréquent dans la petite ville (18,1%) par rapport au milieu rural (25,3%) et à la métropole (37,5%). L’activité physique, plus importante en milieu rural et en petite ville que dans la métropole, était protectrice contre des valeurs élevées d’IMC (ß = -0,145 ; p<0,01), de tour de taille (ß = -0,156 ; p<0,001), de tension systolique (ß = -0,134 ; p<0,01) et diastolique (ß = -0,112, p<0,01), et de triglycérides (ß = -0,098 ; p<0,05). La consommation de légumes était négativement et indépendamment associée à la tension artérielle diastolique (ß = -0,129, p<0,01), alors que celle de poisson était positivement associée au HDL-cholestérol (ß = 0,168 ; p<0,01). L’adéquation en micronutriments était positivement associée au HDL-cholestérol (ß = 0,144; p<0,01) et à un moindre risque de tension artérielle élevée (OR = 0,46 ; IC 95% : 0,26-0,84). L’étude a confirmé l’existence d’un plus grand risque de MCV avec l’urbanisation, un stade plus avancé de transition alimentaire et un mode de vie sédentaire. Ce risque pourrait être réduit par la promotion d’un mode de vie plus actif associé à des apports plus adéquats en micronutriments et une consommation élevée de poisson et de légumes. //// / The purpose of this study was to describe the nutrition transition and its links with cardiovascular disease (CVD) risk factors in a small-size city of Benin and its rural outskirts, and to compare in this regard, the small-size city and the rural area with the major city. A sample of 541 apparently healthy subjects aged 25-60 years was randomly selected from Ouidah, a small-size city of Benin (n = 171), the rural outskirts of Ouidah (n = 170), and Cotonou, the major city (n= 200). Dietary intake and physical activity were assessed with three non consecutives 24-hour recalls. Socioeconomic data were collected by questionnaire. Dietary quality was assessed using a dietary diversity score, a micronutrient adequacy score and a healthfulness score. Blood pressure was measured. Anthropometric measurements were taken. Blood samples were collected to determine serum lipid profile and plasma glucose. A more advanced stage of dietary transition was observed in the major city, which was characterised by higher intakes of meat, milk products, eggs, vegetables and oils, but lower intakes of cereal, fish, legumes, fruit and fibre than the small-size city and the rural area. Dietary diversity was higher in the major city, while micronutrient adequacy and healthfulness scores were lower compared to the small city and the rural area. There was no significant difference in diet and diet quality scores between the small-size city and the rural area. Socioeconomic factors had a strong influence on diet and its quality in the major city. A positive gradient from the rural area to the small-size city to the major city was observed in the prevalence of overall obesity (18%, 12.3%, 8.8%, p = 0.031), abdominal obesity (28.2%, 41.5%, 52.5%; P<0,001) and the metabolic syndrome (4.1%; 6.4%; 11%; p = 0.035) according to the International Diabetes Federation criteria. The prevalence of elevated blood pressure was high, but did not differ across sites (24.1%, 21.6%, 26.5% for rural, small-size city and major city, respectively). The prevalence of low HDL-cholesterol was lower in the small-city (18.1%) compared to the rural area (25.3%) and the major city (37.5%), while fasting plasma glucose was more highly prevalent in the small city (14.6%) and the rural area (10%) compared to the major city (4%). Elevated triglycerides were uncommon. Physical activity was higher in the rural area and small-size city than in the major city, and it was protective against elevated body mass index (ß = -0.145; p<0.01), waist circumference (ß = -0.156; p<0.001), systolic (ß = -0.134; p<0.01) and diastolic (ß = -0.112, p<0.01) blood pressure, and triglycerides (ß = -0,098; p<0,05). Vegetable intakes were negatively and independently associated with diastolic blood pressure, while fish intake was positively associated with HDL-cholesterol. Micronutrient adequacy score was positively associated with HDL-cholesterol (ß = 0,144; p<0,01) and with a lower likelihood of high blood pressure (OR = 0.46; CI 95%: 0.26-0.84). The study confirmed a higher CVD risk with urbanization, advanced stage of dietary transition and a sedentary lifestyle. This risk could be curtailed by improving micronutrient adequacy and increasing vegetables and fish consumption, and by promoting an active lifestyle. / Ce travail a été réalisé avec l'appui du Centre Collaborateur de l'OMS sur la Transition Nutritionnelle et le Développement (TRANSNUT) de l'Université de Montréal, en collaboration avec deux parténaires du Bénin: l'Institut de Sciences Biomédicales Appliquées (ISBA) de Cotonou et l'Institut Régional de Santé Publique de Ouidah.

By the year 2025, it is anticipated that over 300 million individuals world wide will have type 2 diabetes, with a projected increase from 84 to 288 million (170%) in developing countries and from 51 to 72 million (42%) in developed countries. Diabetes leads to a markedly increased risk of heart disease and renal failure and to expensive and debilitating retinopathy and neuropathy. Cognitive decline is also increased. As there is accumulating evidence of the beneficial effects of moderate carbohydrate, low fat dietary patterns compared to high carbohydrate diets, this thesis will focus on the effects of moderate carbohydrate high protein dietary patterns (total carbohydrate: protein: fat ratio of 40%:34%:26%) on glycemic control, risk factors for macrovascular disease and cognitive function. Information on two key areas in type 2 diabetes will be presented, 1. Acute effects of dietary patterns, moderately carbohydrate restricted and high in protein on glucose levels assessed using continuous glucose monitoring systems (CGMS) with verification of these results through a small repeat study. 2. Chronic effects of energy restricted dietary patterns, moderately carbohydrate restricted and high in protein on glucose levels, HbA1c, cognitive function, cardiovascular disease (CVD) risk markers and renal function. In the acute study, we recruited 23 subjects with type 2 diabetes. The participants were randomized to each of 4, 3-day interventions in a cross over design with a 4 day wash out period in which the carbohydrates were distributed differently at each meal; carbohydrates evenly distributed across the day, or carbohydrates loaded at breakfast, lunch or dinner. Glucose levels were continuously measured using CGMS. Outcomes were assessed by postprandial peak glucose (Gmax), time spent above 12 mmol/L (T>12) and total area under the glucose curve (AUC20). The intervention showed that an even distribution of carbohydrates did not optimise blood glucose control, whereas carbohydrates loaded at the lunch time meal provided the most favourable postprandial profile. To verify these results we conducted a repeat study. Six of the previous participants accepted the invitation to return and complete the even distribution arm of the study after a 20 week time lag. The intervention showed that although HbA1c, fasting blood glucose (FBG), AUC, exercise and ambient temperature remained constant there was a significant effect of change in sunlight hours on Gmax, suggesting an effect of sunlight. To assess the chronic effects of energy restricted dietary patterns on the determinants of HbA1c, cognitive function, CVD risk markers and renal function under conditions of weight loss, we recruited 82 participants with type 2 diabetes. These participants were randomised to one of two high protein energy restricted dietary patterns that differed in cholesterol content, for a 12 week period, in a parallel design. A sub group of these participants completed cognitive function testing with (n=34) or without (n=17) CGMS at baseline and at 8 weeks. After 8 weeks of the intervention the determinants of HbA1c under conditions of energy restriction were evaluated. The intervention showed the change in FBG accounted for most of the variance in change in HbA1c, but % energy reduction also contributed independently of FBG. Both energy restricted high protein diets equally improved glycemic control, particularly T>12, AUC, HbA1c and FBG. Fifty one participants completed cognitive testing to evaluate the effect of weight loss and blood glucose control on cognition. Cognitive function was not altered by time, diet, baseline lipid levels. Working memory was predicted by FBG. Short term memory was predicted by FBG, Gmax and AUC24. Sixty five participants completed 12 weeks of the intervention to assess CVD risk markers and renal function. Renal function was maintained and CV markers improved on both dietary patterns, with greatest improvement in HDL-C observed in the group consuming a high protein, energy restricted dietary pattern, high in dietary cholesterol. In conclusion, in the context of a high protein, carbohydrate restricted dietary pattern, cognitive function and renal function did not change, while glycemia and CV risk profiles improved with weight loss over the short term. Under conditions of energy balance diurnal glucose profiles were optimal when the carbohydrates were loaded in the lunch meal. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1342253 / Thesis (Ph.D.) - University of Adelaide, School of Molecular and Biomedical Science, 2008

By the year 2025, it is anticipated that over 300 million individuals world wide will have type 2 diabetes, with a projected increase from 84 to 288 million (170%) in developing countries and from 51 to 72 million (42%) in developed countries. Diabetes leads to a markedly increased risk of heart disease and renal failure and to expensive and debilitating retinopathy and neuropathy. Cognitive decline is also increased. As there is accumulating evidence of the beneficial effects of moderate carbohydrate, low fat dietary patterns compared to high carbohydrate diets, this thesis will focus on the effects of moderate carbohydrate high protein dietary patterns (total carbohydrate: protein: fat ratio of 40%:34%:26%) on glycemic control, risk factors for macrovascular disease and cognitive function. Information on two key areas in type 2 diabetes will be presented, 1. Acute effects of dietary patterns, moderately carbohydrate restricted and high in protein on glucose levels assessed using continuous glucose monitoring systems (CGMS) with verification of these results through a small repeat study. 2. Chronic effects of energy restricted dietary patterns, moderately carbohydrate restricted and high in protein on glucose levels, HbA1c, cognitive function, cardiovascular disease (CVD) risk markers and renal function. In the acute study, we recruited 23 subjects with type 2 diabetes. The participants were randomized to each of 4, 3-day interventions in a cross over design with a 4 day wash out period in which the carbohydrates were distributed differently at each meal; carbohydrates evenly distributed across the day, or carbohydrates loaded at breakfast, lunch or dinner. Glucose levels were continuously measured using CGMS. Outcomes were assessed by postprandial peak glucose (Gmax), time spent above 12 mmol/L (T>12) and total area under the glucose curve (AUC20). The intervention showed that an even distribution of carbohydrates did not optimise blood glucose control, whereas carbohydrates loaded at the lunch time meal provided the most favourable postprandial profile. To verify these results we conducted a repeat study. Six of the previous participants accepted the invitation to return and complete the even distribution arm of the study after a 20 week time lag. The intervention showed that although HbA1c, fasting blood glucose (FBG), AUC, exercise and ambient temperature remained constant there was a significant effect of change in sunlight hours on Gmax, suggesting an effect of sunlight. To assess the chronic effects of energy restricted dietary patterns on the determinants of HbA1c, cognitive function, CVD risk markers and renal function under conditions of weight loss, we recruited 82 participants with type 2 diabetes. These participants were randomised to one of two high protein energy restricted dietary patterns that differed in cholesterol content, for a 12 week period, in a parallel design. A sub group of these participants completed cognitive function testing with (n=34) or without (n=17) CGMS at baseline and at 8 weeks. After 8 weeks of the intervention the determinants of HbA1c under conditions of energy restriction were evaluated. The intervention showed the change in FBG accounted for most of the variance in change in HbA1c, but % energy reduction also contributed independently of FBG. Both energy restricted high protein diets equally improved glycemic control, particularly T>12, AUC, HbA1c and FBG. Fifty one participants completed cognitive testing to evaluate the effect of weight loss and blood glucose control on cognition. Cognitive function was not altered by time, diet, baseline lipid levels. Working memory was predicted by FBG. Short term memory was predicted by FBG, Gmax and AUC24. Sixty five participants completed 12 weeks of the intervention to assess CVD risk markers and renal function. Renal function was maintained and CV markers improved on both dietary patterns, with greatest improvement in HDL-C observed in the group consuming a high protein, energy restricted dietary pattern, high in dietary cholesterol. In conclusion, in the context of a high protein, carbohydrate restricted dietary pattern, cognitive function and renal function did not change, while glycemia and CV risk profiles improved with weight loss over the short term. Under conditions of energy balance diurnal glucose profiles were optimal when the carbohydrates were loaded in the lunch meal. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1342253 / Thesis (Ph.D.) - University of Adelaide, School of Molecular and Biomedical Science, 2008