<b>Background</b> Cardiovascular risk scores are used to estimate absolute risk of disease and identify patients who will benefit most from treatments to lower risk. As a key risk factor for cardiovascular disease, blood pressure is accounted for in many risk scores, but is inherently variable and may be influenced by both biological and measurement factors. This thesis aims to determine how routinely collected blood pressure measurements should best be used for accurate estimation of cardiovascular risk. <b>Methods</b> This thesis describes four main studies. A patient survey and prospective study establish the current practice of blood pressure measurement. Secondary analyses of data from blood pressure monitoring trials determine how risk estimates may be affected by the use of different summary measures of blood pressure. A systematic review evaluates the evidence of an association between blood pressure variability and cardiovascular risk. Finally, a cohort study in the Clinical Practice Research Datalink determines if inclusion of blood pressure variability in cardiovascular risk scores may improve risk estimation. <b>Results</b> Current practice of blood pressure measurement may differ from that in risk score derivation studies. However, these differences have limited effects on cardiovascular risk estimates with few patients reclassified across risk thresholds. Increased long-term variability in blood pressure is in itself a risk factor for cardiovascular disease over and above mean blood pressure but its inclusion in a cardiovascular risk score does not materially improve the accuracy of risk estimates. <b>Conclusions</b> Healthcare professionals should continue to estimate risk for primary prevention of cardiovascular disease using the blood pressure measurements available to them, whether measured at home or in the clinic. There is also no additional benefit of considering measures of long-term blood pressure variability in risk estimation.

abstract: Among the general US population, cardiovascular disease (CVD) is the main cause of mortality for Mexican-Americans. CVD is less prevalent among Mexican-Americans than non-Hispanic Whites or African Americans. However, there is limited research regarding the factors associated with increased CVD risk among Mexican-Americans. Thus, this cross-sectional study was conducted to evaluate the effects of non-biological factors (income, education, employment, acculturation) and diet on CVD risk factors in 75 Mexican-American adults (26 males, 49 females; age=37.6±9.3 y, BMI=28.9±5.3 kg/m2, systolic BP=117±11 mmHg, diastolic BP=73±9 mmHg, LDL cholesterol=114±32 mg/dL, HDL cholesterol=44±11 mg/dL, triglycerides=115±61 mg/dL, serum glucose=92±7 mg/dL). Aside from collecting anthropometric measurements, blood pressure, and measuring fasting blood lipids, glucose, and insulin, information about participants' socioeconomic status, income, employment, education, and acculturation were gathered using a survey. Diet data was collected using the Southwestern Food Frequency Questionnaire. Weight, BMI, and waist circumference were significantly greater for those with a monthly income of <$3000 than for those earning >$3000 (81±15 kg vs. 71±15 kg; 29.8±4.6 kg/m2 vs. 26.5±5.1 kg/m2; 98±12 cm vs. 89±14 cm; respectively) and with an education level of high school graduate or less than for those with some college (84±16 kg vs. 72±14 kg; 30.6±4.2 kg/m2 vs. 26.9±4.9 kg/m2; 100±11 cm vs. 91±13 cm; respectively). HDL-C was higher for those with a monthly income of >$3000 than those earning <$3000 (49±12 mg/dL vs. 41±10 mg/dL), those with some college education than those with high school or less (47±10 mg/dL vs. 37±9 mg/dL), and for those employed than those not employed (46±10 mg/dL vs. 40±12 mg/dL). There was no association between acculturation and CVD risk factors. Percent of energy consumed from fat was greater and percent of energy from carbohydrates was lower in those earning <$3000 monthly than those earning >$3000 (32±5% vs. 29±3%; 52±8% vs. 56±4%; respectively). Greater acculturation to the Anglo culture was negatively correlated with body fat percentage (r=-0.238, p=0.043) and serum glucose (r=-0.265, p=0.024). Overall, these results suggest that factors related to sociocultural and socioeconomic status may affect cardiometabolic disease risk in Mexican-Americans living in the Phoenix metropolitan area. / Dissertation/Thesis / M.S. Nutrition 2011

The thesis is focused on the lifestyle of people with elevated cholesterol level. Fundamental terms, which are basic for the topic, are explained. The latest findings stated in professional literature on lifestyle, health, diseases, health promotion and health prevention are presented. The most recent statistical results are mentioned The first section of the thesis is focused on the issue in general, i.e. on lifestyle, the definition of health and its determinants, nutrition and stress. A large section is devoted to determinants of health that significantly affect human health. These are healthcare, genetics, environmental impacts. Therefore, the great importance of our lifestyle, which may be influenced by smoking, stress, physical activity, drug use, alcohol consumption and diet, is demonstrated. A large part of our activities can be positively influenced by ourselves. The determinants and their effects on human body are mentioned. The main focus is put on diseases associated with elevated cholesterol levels, where cardiovascular disease stands first. Another aspect makes a positive side and this is healthy lifestyle. Healthy lifestyle and practices how to positively influence our health are characterized. A specific decalogue, giving certain constrains, is outlined. And also the irreplaceable role of prevention and health promotion, which is one of activities of the public health protection authorities, is mentioned. The projects of the World Health Organization also contribute to the population health promotion. The project Health 21 is also mentioned in this thesis. The objective of this study was to analyze the results of cholesterol tests in the framework of a screening program in the South Bohemian Region carried out over the period of three years. A sub-objective was to determine the lifestyle changes in clients with the decrease in blood cholesterol levels. The main hypothesis is ? there is a rising trend in elevated cholesterol levels in the blood In the practical section the results obtained from the qualitative research focused on the lifestyle of people with elevated cholesterol levels are presented. The issues concerning their lifestyle such as physical activity, stress, smoking, dietary habits, fluid intake and sleep are investigated. The questionnaire survey and the subsequent analysis of the data obtained have shown that these persons have a more responsible approach to their lifestyle. They admit that the results of the tests focused on cholesterol levels positively affect their lifestyle. The majority of respondents positively affect their lifestyle according to theoretical recommendations. Comprehensive investigation has proved that the overall lifestyle is comparable to the general population.

La nutrition est l’un des facteurs environnementaux modifiables pouvant avoir un rôle majeur dans la prévention des maladies cardiovasculaires (MCV). Dans ce cadre, un intérêt croissant a été porté ces dernières décennies aux polyphénols, des composés bioactifs potentiellement protecteurs. L’objectif général du travail de cette thèse était l’étude du lien entre la qualité de l’alimentation et les MCV, à partir des données issues des cohortes françaises SU.VI.MAX et NutriNet-Santé. Le premier objectif était d’étudier l’association prospective entre un score individuel mesurant la qualité globale de l’alimentation (score FSA-NPS DI) et le risque de MCV. Le second objectif était d’étudier les associations entre les apports alimentaires en polyphénols et le risque de MCV ainsi que la variation du statut pondéral, en utilisant la table de composition Phenol-Explorer®. Enfin, le troisième objectif était de comparer les consommations et les comportements alimentaires des participants de l’étude NutriNet-Santé présentant une MCV ou un trouble cardiométabolique à des témoins. Concernant le premier objectif, nos résultats indiquaient que des choix alimentaires de moindre qualité nutritionnelle, comme reflété par un score FSA-NPS DI plus élevé, étaient associés à une augmentation de risque de MCV, en particulier chez les individus en surpoids ou obèses dans la cohorte NutriNet-Santé et les fumeurs et ceux ayant un faible niveau d’activité physique dans la cohorte SU.VI.MAX. Concernant le deuxième objectif, nos résultats indiquaient que les anthocyanines, les catéchines, les flavonols, les dihydrochalcones, les dihydroflavonols, les acides hydroxybenzoiques et les stilbènes étaient associés à une moindre survenue des MCV. Nos résultats indiquaient également qu'un apport plus élevé en polyphénols totaux ainsi qu'un apport plus élevé en flavones, flavanones, proanthocyanidines, lignanes et acides hydroxycinnamiques étaient associés à une moindre augmentation de l’adiposité au cours du suivi. Concernant le troisième objectif, nous avons montré, que les adultes, présentant une maladie cardiovasculaire ou cardio-métabolique avaient des comportements moins favorables pour la santé que des témoins du même âge et sexe. Nous avons ainsi mis en évidence les aspects nutritionnels sur lesquels il serait stratégique d’axer en priorité les efforts de prévention et d’accompagnement des patients afin d’améliorer la prise en charge des maladies cardio-métaboliques et cardiovasculaires après leur diagnostic. En conclusion, les résultats de cette thèse ont contribué à une meilleure compréhension du rôle potentiel des facteurs nutritionnels dans l’étiologie des maladies cardiovasculaires via une approche holistique et plus spécifique pour les polyphénols. Cette thèse offre des pistes de réflexion pour les futures stratégies en prévention primaire, secondaire et tertiaire des maladies cardiovasculaires. / Nutrition is one of the modifiable environmental factors that may have a major role in the prevention of cardiovascular diseases (CVD). In this context, in etiological epidemiology, there has been a growing interest in polyphenols – bioactive components that are potentially protective. Hence, the general objective of the work presented in this thesis was to study the link between the quality of the diet and CVD, based on data from the French cohorts SU.VI.MAX and NutriNet-Santé.The first objective was to study the prospective association between an individual score measuring the overall quality of the diet (the FSA-NPS DI) and CVD risk, in the context of a French national primary prevention strategy aiming to apply a coloured front-of-package label (the 5C label). The second objective was to examine the association of dietary intakes of different polyphenols with CVD risk and with weight change, using the Phenol-Explorer® composition table. Finally, the third objective was to compare the food and nutrient consumptions and lifestyle behaviours of NutriNet-Santé participants presenting a CVD or a cardiometabolic disorder with those of ‘control’ participants. Concerning the first objective, our results indicated that the choice of foods of a lower nutritional quality, as reflected by a higher FSA-NPS DI score, was associated with an increase in CVD risk – in particular among overweight or obese participants of the NutriNet-Santé cohort, and among participants of the SU.VI.MAX cohort that were smokers or had a low physical activity level. Concerning the second objective, our results indicated that anthocyanins, catechins, flavonols, dihydrochalcones, dihydroflavonols, hydroxybenzoic acids, other phenolic acids and stilbenes were associated with a lower CVD risk. Our results also indicated that a higher intake of total polyphenols as well as a higher intake of falvones, flavanones, proanthocyanins, lignans and hydroxycinnamic acids was associated with a less pronounced increase in body mass index and waist circumference over 6 years. Concerning the third objective, we have shown that adults presenting a CVD or a cardiometabolic disorder had less beneficial behaviours than control participants of the same age and sex, in terms of physical activity, smoking status, and the consumption of alcohol, fruits and vegetables, whole grain cereals, of meat and particularly of processed meat. In addition, we have observed a lower intake of most polyphenol categories among patients. Our results thus provide indications on the nutritional elements that should be at the centre of secondary and tertiary prevention strategies, so as to improve the treatment of CVD and cardiometabolic dysfunctions once that they are diagnosed.To conclude, this thesis contributes to a better understanding of the role of nutritional factors in the development of CVD, using both holistic and specific (through polyphenols) approaches. These results are of interest for future prevention strategies that aime at reducing the risks of CVD through nutrition.

Natural therapies such as Aged Garlic Extract (AGE) have displayed cardioprotective properties, with studies indicating that AGE can inhibit platelet aggregation both in vivo and in vitro. The mechanism of inhibition induced by AGE is proposed to be due to AGE exerting effects upon several targets within platelets, including calcium and cyclic adenosine monophosphate (cAMP). The effect of AGE upon the other cyclic nucleotide, cyclic guanosine monophosphate (cGMP) is currently unknown. The aims therefore of this project are to identify the effect of AGE upon platelet cGMP, as well as associated signaling molecules including nitric oxide (NO) and cAMP.It was found that the NO donor 3-morpholinosydnonimine (Sin-1) in high concentrations along with the presence of specific inhibitors inhibited platelet aggregation independently of cGMP. Experimentation using chemical inhibitors also displayed erratic results in the presence of high concentrations of AGE, indicating that AGE was influencing the binding of such inhibitors. The results of in vitro experiments indicated that AGE moderately increases intraplatelet cGMP, whereas intraplatelet cAMP is significantly increased. it is proposed that the main mechanism of inhibition caused by AGE is due to increases in cAMP. As intraplatelet cAMP can also be influenced by intraplatelet cGMP, it is likely that cAMP is increased directly and indirectly by AGE.Evidence provided in the present study supports the proposed theory that the mechanisms of inhibition of platelet aggregation by AGE is multimechanistic. More specifically inhibition of platelet aggregation by AGE is due to AGE increasing intraplatelet cyclic nucleotides, reducing the expression of key receptors such as GPIIb/IIIa and inhibiting agonist induced platelet shape change. As AGE can inhibit platelet aggregation, which is a key risk factor in cardiovascular disease, the consumption of AGE would be beneficial to those who are at risk of cardiovascular episodes.

Preventing cardiovascular diseases (CVD) is one of the main components of preventive medicine. This thesis deals with prevention of cardiovascular diseases. The theoretical part describes the pathogenesis of atherosclerosis, which is at the background of 90 % of CVD. The next chapters deal with the most common cardiovascular disease and its risk factors. There is described determination of cardiovascular risk and a nutritional prevention is included at the end of the theoretical part. A part of this work is a research carried out on 107 randomly selected individuals. The main objective was to find out the level of knowledge of this individuals about the possibilities of prevention of cardiovascular diseases. The survey was performed in a questionnaire survey, both in electronic and printed form. The survey revealed that the majority of respondents (87,9 %) correctly associate the CVD with an inappropriate lifestyle, only 12,1 % of respondents considered the most important factor in genetics. The negative influence of inappropriate meals and lack of physical activity prevails in the respondents' awareness. Most respondents also correctly stated that CVD accounts for almost 50 % of all deaths in the Czech Republic. An active interest in lifestyle, which is an integral part of preventive measures,...

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Objetivo: Avaliar o estado nutricional e o risco de doença cardiovascular (DCV) de mulheres no climatério. Metodologia: Estudo transversal, cuja população foi composta por 200 mulheres de 35 a 65 anos, agrupadas de acordo com a fase do climatério: pré-menopausa (PRÉ), perimenopausa (PERI) e pós-menopausa (PÓS). As mulheres do grupo PÓS foram divididas em dois grupos: sem terapia de reposição hormonal (S/TRH) e com TRH oral por no mínimo 12 meses (C/TRH). O estado nutricional foi avaliado segundo o índice de massa corporal (IMC) e o percentual de gordura corporal (%GC); o risco de DCV foi avaliado segundo a relação cintura/quadril (RCQ). O nível de significância utilizado nas análises foi alfa=5%. Resultados: A prevalência de pré-obesidade + obesidade, segundo o IMC, foi 65,4% (PRÉ), 70,9% (PERI) e 67,4% (PÓS), porém não houve diferença significativa entre os grupos. Comparado ao grupo C/TRH, houve maior proporção de mulheres obesas no grupo S/TRH (p=0,04), 21,4% e 48,4%, respectivamente. O %GC revelou sobrepeso e obesidade em 50,7% (PRÉ), 66,7% (PERI) e 57,4% (PÓS); 67,7% (S/TRH) e 54,8% (C/TRH) – essas diferenças não foram estatisticamente significativas. O risco de DCV foi considerado alto e muito alto para a maioria das mulheres: 90,7% (PRÉ), 95,8% (PERI) e 84,1% (PÓS); 90,3% (S/TRH) e 76,2% (C/TRH) e não houve diferença estatística entre os grupos. Conclusão: Grande parte das mulheres apresentou alto risco de afecções relacionadas à obesidade, como a DCV, justificando a atenção à mulher no climatério para a prevenção das principais causas de mortalidade nesse grupo. / Purpose: To evaluate the nutritional status and cardiovascular disease (CVD) risk of climacteric women. Methodology: Transversal study, composed by 200 women aged 35-65 years, grouped according to the climacteric stage: premenopause (PRE), perimenopause (PERI) and postmenopause (POS). The PÓS group was divided in two groups: with no hormonal replacement therapy (N/HRT) and with oral HRT for at least 12 months (W/HRT). The nutritional status was assessed by body mass index (BMI) and body fat percentage (BF%); the CVD risk was assessed by waist hip ratio (WHR). The significance level used for the analyses was alpha=5%. Results: According to BMI, the pre-obesity + obesity prevalences were 65,4% (PRÉ), 70,9% (PERI) e 67,4% (POS) and there was no significant difference among these groups. Compared with the group W/HRT, there was a higher rate (p=0,04) of obesity among women in the N/HRT group: 21,4% and 48,4%, respectively. The BF% showed overweight and obesity in 50,7% (PRE), 66,7% (PERI) and 57,4% (POS); 67,7% (N/TRH) and 54,8% (W/TRH), differences that were not statisticaly significant. In all groups there was a greater proportion of women considered with high and very high risk of CVD: 90,7% (PRE), 95,8% (PERI) and 84,1% (POS); 90,3% (N/TRH) and 76,2% (W/TRH) and the risk did not differ statisticaly among the groups. Conclusion: The majority of women had increased obesity-related and cardiovascular disease risk, emphasizing women´s health attention programms to the prevention of the leading mortality causes in this group.

Cardiovascular disease is a leading cause of death worldwide and becomes increasingly prevalent in the elderly population. Independent of etiopathogenesis, heart failure (HF) is the final common stage of numerous heart diseases. Cardiac stem cell (CSC) therapy has emerged as a promising cell-based strategy for treatment of HF. However, cell replacement is not able to fully restore a structurally damaged myocardium in advanced and end-stage HF. The objective of this project was to test the following hypotheses: that a bioengineered heart extracellular matrix (ECM) with preserved intact geometric structure could be generated using decellularization by coronary perfusion; and that autologous CSCs, to repopulate this ECM, could be isolated and expanded from the adult heart, with the caveat that autologous CSCs are depleted and impaired by both aging and chronic dilated cardiomyopathy. This will help to develop a possible therapeutic approach for advanced HF, using a combination of CSCs and engineering technique. Resident CSCs were isolated from explant-derived cells (EDCs) and expanded into cardiosphere-derived cells (CDCs) via cardiosphere formation. The CDCs expressed CSC markers (c-kit and Sca-1), pluripotent markers (Oct3/4 and Sox2), and the cardiac lineage-committed marker (Nkx2.5), and showed clonal expansion, self-renewal, and cardiomyogenic potential in vitro. In tissue engineering experiments, CDCs survived and proliferated within biomaterial alginate scaffolds for up to 7 weeks. An engineered bioartificial ECM scaffold was successfully produced from a whole rat heart using retrograde coronary perfusion and possessed an intact 3D architecture with functionally perfusable vascular network. Compared with ventricles, cultures derived from atria produced significantly higher number of c-kit+ and Sca-1+ CSCs (c-kit: 13% vs. 3.4%; Sca-1: 82% vs. 53%, respectively) and exhibited greater clonogenic and proliferative capacity. CDCs could be grown from young and aged mice, but the yield of CSCs significantly declined with age, as did cell migration and differentiation potential. In comparison to wild-type mice, atrial-CDCs from dystrophic mice showed no significant differences in CSC subpopulations and characteristics, despite confirmation of cardiac dysfunction using MRI. In conclusion, CDCs could be considered to be a viable cell candidate for cardiac therapy and may be used to treat HF at various stages, in combination with myocardial tissue engineering.

Human Immunodeficiency Virus Type I, or HIV, is one of the most well-known and well-researched viruses in the world. The current standard of care for HIV infected individuals is an antiretroviral drug therapy regiment, or ART, started immediately after diagnosis. While this treatment is generally quite effective at keeping the viral load low and stopping the progression from HIV infection to AIDS, patients receiving ART therapy still have a lower life expectancy than uninfected individuals. Many times, the cause of death in these patients is not the common opportunistic pathogens and cancers linked to HIV and AIDS, but chronic health conditions that develop. One of these conditions that is seen in many of the HIV infected patients undergoing the antiretroviral therapy is cardiovascular disease, such as atherosclerosis and myocardial infarction. Research shows that one of the key players in developing these conditions in HIV patients is the chronic inflammation caused by the immune system attempts to control the level of the virus. By studying the links between HIV, inflammation, and cardiovascular disease, we may be able to find solutions to the development of chronic disease in HIV patients on antiretroviral therapy.