INFLUENCE OF 24-HOUR SLEEP DEPRIVATION ON CARDIOVASCULAR AND NEURAL CONTROL AT REST AND DURING ACUTE STRESS IN HUMANS

Recent epidemiological studies report a consistent association between short sleep and incidence of hypertension, as well as short sleep and cardiovascular disease-related mortality. While the association between short sleep and hypertension appears to be stronger in women than men, the mechanisms underlying the relations between sleep deprivation, stress, risks of cardiovascular diseases, and sex remain unclear. We conducted two studies to investigate the underlying neural mechanisms of these relations. In study 1, we examined sympathetic neural and blood pressure responses to experimentally-induced sleep deprivation in men and women. We further investigated the influence of sleep deprivation on cardiovascular reactivity to acute stress. In study 2, we examined the neural and cardiovascular function throughout the ovarian cycle in sleep deprived women. Twenty-eight young healthy subjects (14men and 14 women) were tested twice in study 1, once after normal sleep (NS) and once after 24-h total sleep deprivation (TSD). We measured the blood pressure, heart rate (HR), muscle sympathetic nerve activity (MSNA) and forearm blood flow (FBF) during 10min baseline, 5min of mental stress (MS) and 2 min cold pressor test (CPT). We demonstrated that TSD increased resting arterial blood pressure to a similar extent in both men and women, but MSNA decreased only in men following TSD. This MSNA response was associated with altered baroreflex function in women and divergent testosterone responses to TSD between men and women. Regarding TSD and cardiovascular reactivity, TSD elicited augmented HR reactivity and delayed recovery during both MS and CPT in men and women, and responses between sexes were not statistically different. Fourteen young healthy women participated in study 2. Subjects were tested twice, once during their early follicular (EF) phase after TSD, once during their mid-luteal (ML) phase after TSD. Blood pressure, HR, MSNA, and FBF were recorded during 10min baseline, 5 min MS, and 2 min CPT. We observed an augmented resting supine blood pressure during EF compared to ML in sleep deprived women. In contrast, resting MSNA, as well as cardiovascular responses to stressors, were similar between EF and ML after TSD. In conclusion, we observed sex differences in MSNA responses to TSD that demonstrate reductions of MSNA in men, but not women. TSD elicited augmented HR reactivity and delayed HR recovery to acute stressors similarly in men and women. We also reported an augmented supine blood pressure during EF compared to ML in sleep deprived women. These novel findings provide new and valuable mechanistic insight regarding the complex and poorly understood relations among sleep deprivation, sex, stress, and risk of cardiovascular disease.

Analysis of postprandial lipemia as a Cardiovascular Disease risk factor using genetic and clinical information: an Artificial Neural Network perspective

Clinical studies indicate that exaggerated postprandial lipemia is linked to the progression of atherosclerosis, leading cause of Cardiovascular Diseases (CVD). CVD is a multi-factorial disease with complex etiology and according to the literature postprandial Triglycerides (TG) can be used as an independent CVD risk factor. Aim of the current study is to construct an Artificial Neural Network (ANN) based system for the identification of the most important gene-gene and/or gene-environmental interactions that contribute to a fast or slow postprandial metabolism of TG in blood and consequently to investigate the causality of postprandial TG response. The design and development of the system is based on a dataset of 213 subjects who underwent a two meals fatty prandial protocol. For each of the subjects a total of 30 input variables corresponding to genetic variations, sex, age and fasting levels of clinical measurements were known. Those variables provide input to the system, which is based on the combined use of Parameter Decreasing Method (PDM) and an ANN. The system was able to identify the ten (10) most informative variables and achieve a mean accuracy equal to 85.21%.

Subclinical hypothyroidism and cardiovascular risk: how to end the controversy

The indications for screening and TSH threshold levels for treatment of subclinical hypothyroidism have remained a clinical controversy for over 20 years. Subclinical thyroid dysfunction is a common finding in the growing population of older adults, occurring in 10���15% among those age 65 and older, and may contribute to multiple common problems of older age, including cardiovascular disease, muscular impairment, mood problems, and cognitive dysfunction (1). In 2004, both the U.S. Preventive Services Task Force (2) and a clinical consensus group of experts (3) concluded that the existing evidence about the association between subclinical hypothyroidism and cardiovascular risks, primarily cross-sectional or case-control studies (4), was insufficient. For example, a frequently cited analysis from the Rotterdam study found a cross-sectional association between subclinical hypothyroidism and atherosclerosis, as measured by abdominal aortic calcification (odds ratio, 1.7; 95% confidence interval [CI], 1.1���2.6) and prevalent myocardial infarction (MI) (odds ratio, 2.3; 95% CI, 1.3���4.0) (5). Conversely, the prospective part of this study included only 16 incident MIs; the hazard ratio (HR) for subclinical hypothyroidism was 2.50, with broad 95% CIs (0.70���9.10). Potential mechanisms for the associations with cardiovascular diseases among adults with subclinical hypothyroidism include elevated cholesterol levels, inflammatory markers, raised homocysteine, increased oxidative stress, insulin resistance, increased systemic vascular resistance, arterial stiffness, altered endothelial function, and activation of thrombosis and hypercoagulability that have all been reported to be associated with subclinical hypothyroidism (1, 6).

Concept, design and implementation of a cardiovascular gene-centric 50 k SNP array for large-scale genomic association studies.

A wealth of genetic associations for cardiovascular and metabolic phenotypes in humans has been accumulating over the last decade, in particular a large number of loci derived from recent genome wide association studies (GWAS). True complex disease-associated loci often exert modest effects, so their delineation currently requires integration of diverse phenotypic data from large studies to ensure robust meta-analyses. We have designed a gene-centric 50 K single nucleotide polymorphism (SNP) array to assess potentially relevant loci across a range of cardiovascular, metabolic and inflammatory syndromes. The array utilizes a "cosmopolitan" tagging approach to capture the genetic diversity across approximately 2,000 loci in populations represented in the HapMap and SeattleSNPs projects. The array content is informed by GWAS of vascular and inflammatory disease, expression quantitative trait loci implicated in atherosclerosis, pathway based approaches and comprehensive literature searching. The custom flexibility of the array platform facilitated interrogation of loci at differing stringencies, according to a gene prioritization strategy that allows saturation of high priority loci with a greater density of markers than the existing GWAS tools, particularly in African HapMap samples. We also demonstrate that the IBC array can be used to complement GWAS, increasing coverage in high priority CVD-related loci across all major HapMap populations. DNA from over 200,000 extensively phenotyped individuals will be genotyped with this array with a significant portion of the generated data being released into the academic domain facilitating in silico replication attempts, analyses of rare variants and cross-cohort meta-analyses in diverse populations. These datasets will also facilitate more robust secondary analyses, such as explorations with alternative genetic models, epistasis and gene-environment interactions.

Smooth Muscle Hyperplasia due to ACTA2/MYH11 Mutations: Identification of Novel Pathology and Pathways Leading to Aneurysms and Diverse Vascular Occlusive Diseases

Missense mutations in smooth muscle cell (SMC) specific ACTA2 (��-actin) and MYH11 (��-myosin heavy chain) cause diffuse and diverse vascular diseases, including thoracic aortic aneurysms and dissections (TAAD) and early onset coronary artery disease and stroke. The mechanism by which these mutations lead to dilatation of some arteries but occlusion of others is unknown. We hypothesized that the mutations act through two distinct mechanisms to cause varied vascular diseases: a loss of function, leading to decreased SMC contraction and aneurysms, and a gain of function, leading to increased SMC proliferation and occlusive disease. To test this hypothesis, ACTA2 mutant SMCs and myofibroblasts were assessed and found to not form ��-actin filaments whereas control cells did, suggesting a dominant negative effect of ACTA2 mutations on filament formation. A loss of ��-actin filaments would be predicted to cause decreased SMC contractility. Histological examination of vascular tissues from patients revealed SMC hyperplasia leading to arterial stenosis and occlusion, supporting a gain of function associated with the mutant gene. Furthermore, ACTA2 mutant SMCs and myofibroblasts proliferated more rapidly in static culture than control cells (p<0.05). We also determined that Acta2-/- mice have ascending aortic aneurysms. Histological examination revealed aortic medial SMC hyperplasia, but minimal features of medial degeneration. Acta2-/- SMCs proliferated more rapidly in culture than wildtype (p<0.05), and microarray analysis of Acta2-/- SMCs revealed increased expression of Actg2, 15 collagen genes, and multiple focal adhesion genes. Acta2-/- SMCs showed altered localization of vinculin and zyxin and increased phosphorylated focal adhesion kinase (FAK) in focal adhesions. A specific FAK inhibitor decreased Acta2-/- SMC proliferation to levels equal to wildtype SMCs (p<0.05), suggesting that FAK activation leads to the increased proliferation. We have described a unique pathology associated with ACTA2 and MYH11 mutations, as well as an aneurysm phenotype in Acta2-/- mice. Additionally, we identified a novel pathogenic pathway for vascular occlusive disease due to loss of SMC contractile filaments, alterations in focal adhesions, and activation of FAK signaling in SMCs with ACTA2 mutations.

A longitudinal comparison of cardiovascular disease risk factors among children and adolescents in the U.S. and Japan: Project HeartBeat!

Blood cholesterol and blood pressure development in childhood and adolescence have important impact on the future adult level of cholesterol and blood pressure, and on increased risk of cardiovascular diseases. The U.S. has higher mortality rates of coronary heart diseases than Japan. A longitudinal comparison in children of risk factor development in the two countries provides more understanding about the causes of cardiovascular disease and its prevention. Such comparisons have not been reported in the past. ^ In Project HeartBeat!, 506 non-Hispanic white, 136 black and 369 Japanese children participated in the study in the U.S. and Japan from 1991 to 1995. A synthetic cohort of ages 8 to 18 years was composed by three cohorts with starting ages at 8, 11, and 14. A multilevel regression model was used for data analysis. ^ The study revealed that the Japanese children had significantly higher slopes of mean total cholesterol (TC) and high density lipoprotein (HDL) cholesterol levels than the U.S. children after adjusting for age and sex. The mean TC level of Japanese children was not significantly different from white and black children. The mean HDL level of Japanese children was significantly higher than white and black children after adjusting for age and sex. The ratio of HDL/TC in Japanese children was significantly higher than in U.S. whites, but not significantly different from the black children. The Japanese group had significantly lower mean diastolic blood pressure phase IV (DBP4) and phase V (DBP5) than the two U.S. groups. The Japanese group also showed significantly higher slopes in systolic blood pressure, DBP5 and DBP4 during the study period than both U.S. groups. The differences were independent from height and body mass index. ^ The study provided the first longitudinal comparison of blood cholesterol and blood pressure between the U.S. and Japanese children and adolescents. It revealed the dynamic process of these factors in the three ethnic groups. ^

High-density lipoprotein cholesterol, coronary artery disease, and cardiovascular mortality.

AIMS High-density lipoprotein (HDL) cholesterol is a strong predictor of cardiovascular mortality. This work aimed to investigate whether the presence of coronary artery disease (CAD) impacts on its predictive value. METHODS AND RESULTS We studied 3141 participants (2191 males, 950 females) of the LUdwigshafen RIsk and Cardiovascular health (LURIC) study. They had a mean �� standard deviation age of 62.6 �� 10.6 years, body mass index of 27.5 �� 4.1 kg/m&sup2;, and HDL cholesterol of 38.9 �� 10.8 mg/dL. The cohort consisted of 699 people without CAD, 1515 patients with stable CAD, and 927 patients with unstable CAD. The participants were prospectively followed for cardiovascular mortality over a median (inter-quartile range) period of 9.9 (8.7-10.7) years. A total of 590 participants died from cardiovascular diseases. High-density lipoprotein cholesterol by tertiles was inversely related to cardiovascular mortality in the entire cohort (P = 0.009). There was significant interaction between HDL cholesterol and CAD in predicting the outcome (P = 0.007). In stratified analyses, HDL cholesterol was strongly associated with cardiovascular mortality in people without CAD [3rd vs. 1st tertile: HR (95% CI) = 0.37 (0.18-0.74), P = 0.005], but not in patients with stable [3rd vs. 1st tertile: HR (95% CI) = 0.81 (0.61-1.09), P = 0.159] and unstable [3rd vs. 1st tertile: HR (95% CI) = 0.91 (0.59-1.41), P = 0.675] CAD. These results were replicated by analyses in 3413 participants of the AtheroGene cohort and 5738 participants of the ESTHER cohort, and by a meta-analysis comprising all three cohorts. CONCLUSION The inverse relationship of HDL cholesterol with cardiovascular mortality is weakened in patients with CAD. The usefulness of considering HDL cholesterol for cardiovascular risk stratification seems limited in such patients.

South Asian immigrant cardiovascular risk assessment in Houston, Texas 2005

Background. Heart disease is the leading cause of death and stroke is the third leading cause of deaths for all people in the United States. South Asian Americans have a higher risk of developing cardiovascular diseases than native United States residents. ^ Purpose. This study examines the cardiovascular risk factors in the South Asian immigrant community residing in Southwest Houston. This study also explores the level of health insurance available to the South Asian in Houston. ^ Methods. One hundred sixty-two South Asian patients aged 18 years and older received cardiovascular screening from January 1 st, 2005 to March 31st, 2005 at Ibn Sina Community Clinic; blood pressure was measured twice in both arms after resting five minutes. Height and weight were also recorded. Demographic data was collected through personal interview (questionnaire) and blood samples were drawn to collect laboratory data. ^ Results. There were 162 eligible South Asian patients, among whom 127 (78%) participated in the study. There were no significant differences between the responders and the non-responders in terms of demographics and clinical characteristics. Laboratory data revealed a mean total cholesterol of 201 �� 34 mg/dl, 54 percent had high total cholesterol above 200 mg/dl. The mean fasting glucose was 108 �� 43 mg/dl, and body mass index (BMI) was 28 �� 4 kg/m2. The prevalence of hypertension was comparable with the general U.S. population; 38 percent of the South Asian males and 29 percent of females had hypertension. The prevalence of diabetes was also compared; 21 percent of SA males (3% for white American males) and 7 percent of SA females (2% for white American females) were found to have undiagnosed diabetes. Of the sample 12 percent had both hypertension and diabetes; 21 percent had both hypertension and high BMI, and 19 percent had hypertension and high total cholesterol levels. ^ Conclusion. The present study shows that the South Asians in this sample are at greater risk of developing cardiovascular diseases than other ethnicities. The high prevalence of hypertension, type 2 diabetes, higher total cholesterol levels with overweight and obesity, and less leisure time physical activity are important cardiovascular risk factors for South Asians population. ^

Adipocitoquinas y s��ndrome metab��lico : rol de la vistafina en la patogenia de enfermedad cardiovascular

La enfermedad cardiovascular es la primera causa de morbi-mortalidad en los pa��ses industrializados. El s��ndrome metab��lico, caracterizado por hipertensi��n, dislipidemia, obesidad e hiperglucemia, constituye el principal factor de riesgo para la enfermedad cardiovascular. El tejido adiposo visceral juega un papel fundamental en este proceso, dado que secreta una variedad de sustancias biol��gicamente activas denominadas adipoquinas o adipocitoquinas, tales como leptina, resistina, adiponectina, factor de necrosis tumoral alfa (TNFa), y visfatina entre otras. La visfatina es una citoquina descubierta recientemente y su rol en la enfermedad cardiovascular es controversial y a��n no ha sido completamente dilucidado. Estudios realizados en humanos y en modelos experimentales en animales sugieren que la visfatina tendr��a un papel muy importante en las patolog��as asociadas a la enfermedad cardiovascular. Esta revisi��n intenta mostrar los ��ltimos avances sobre el rol de la visfatina y las principales adipocitoquinas en las patolog��as cardiovasculares y el s��ndrome metab��lico.

Evolution and treatment of vitamin B12 deficiency as a risk factor for (cognitive and functional) neurodegenerative diseases in institutionalized elderly = Evoluci��n y tratamiento de la deficiencia de vitamina B12 como factor de riesgo de enfermedades neurodegenerativas (cognitivas y funcionales) en las personas mayores institucionalizadas.

Prevalence of vitamin B12 deficiency is very common in elderly people and can reach values as high as 40.5% of the population. It can be the result of the interaction among several factors. Vitamin B12 deficiencies have been associated with neurological, cognitive deterioration, haematological abnormalities and cardiovascular diseases that have an important influence on the health of the elderly and their quality of life. It is necessary to approach the problems arisen from the lack of data relative to them. The main objective of this thesis was to analyse the evolution of vitamin B12 status and related parameters, lipid and haematological profiles and their relationship to health risk factors, and to functional and cognitive status over one year and to determine the effect of an oral supplementation of 500 ��g of cyanocobalamin for a short period of 28 days. An additional objective was to analyze the possible effects of medicine intakes on vitamin B status. Three studies were performed: a) a one year longitudinal follow-up with four measure points; b) an intervention study providing an oral liquid supplement of 500 ��g of cyanocobalamin for a 28 days period; and c) analysis of the possible effect of medication intake on vitamin B status using the ATC classification of medicines. The participants for these studies were recruited from nursing homes for the elderly in the Region of Madrid. Sixty elders (mean age 84 _ 7y, 19 men and 41 women) were recruited for Study I and 64 elders (mean age 82 _ 7y, 24 men and 40 women) for Study II. For Study III, baseline data from the initially recruited participants of the first two studies were used. An informed consent was obtained from all participants or their mentors. The studies were approved by the Ethical Committee of the University of Granada. Blood samples were obtained at each examination date and were analyzed for serum cobalamin, holoTC, serum and RBC folate and total homocysteine according to laboratory standard procedures. The haematological parameters analyzed were haematocrit, haemoglobin and MCV. For the lipid profile TG, total cholesterol, LDL- and HDLcholesterol were analyzed. Anthropometric measures (BMI, skinfolds [triceps and subscapular], waist girth and waist to hip ratio), functional tests (hand grip, arm and leg strength tests, static balance) and MMSE were obtained or administered by trained personal. The vitamin B12 supplement of Study II was administered with breakfast and the medication intake was taken from the residents��� anamnesis. Data were analyzed by parametric and non-parametric statistics depending on the obtained data. Comparisons were done using the appropriate ANOVAs or non-parametric tests. Pearsons��� partial correlations with the variable ���time��� as control were used to define the association of the analyzed parameters. XIII The results showed that: A) Over one year, in relationship to vitamin B status, serum cobalamin decreased, serum folate and mean corpuscular volumen increased significantly and total homocysteine concentrations were stable. Regarding blood lipid profile, triglycerides increased and HDL-cholesterol decreased significantly. Regarding selected anthropometric measurements, waist circumference increased significantly. No significant changes were observed for the rest of parameters. B) Prevalence of hyperhomocysteinemia was high in the elderly studied, ranging from 60% to 90 % over the year depending on the cut-off used for the classification. LDL-cholesterol values were high, especially among women, and showed a tendency to increase over the year. Results of the balance test showed a deficiency and a tendency to decrease; this indicates that the population studied is at high risk for falls. Lower extremity muscular function was deficient and showed a tendency to decrease. A highly significant relationship was observed between the skinfold of the triceps and blood lipid profile. C) Low cobalamin concentrations correlated significantly with low MMSE scores in the elderly studied. No correlations were observed between vitamin B12 status and functional parameters. D) Regarding vitamin B12 status, holo-transcobalamin seems to be more sensitive for diagnosis; 5-10% of the elderly had a deficiency using serum cobalamin as a criterion, and 45-52% had a deficiency when using serum holotranscobalamin as a criterion. E) 500 ��g of cyanocobalamin administered orally during 28 days significantly improved vitamin B12 status and significantly decreased total homocysteine concentrations in institutionalized elderly. No effect of the intervention was observed on functional and cognitive parameters. F) The relative change (%) of improvement of vitamin B12 status was higher when using serum holo-transcobalamin as a criterion than serum cobalamin. G) Antiaenemic drug intake normalized cobalamin, urologic drugs and corticosteroids serum folate, and psychoanaleptics holo-transcobalamin levels. Drugs treating pulmonary obstruction increased total homocysteine concentration significantly. H) The daily mean drug intake was 5.1. Fiftynine percent of the elderly took medication belonging to 5 or more different ATC groups. The most prevalent were psycholeptic (53%), antiacid (53%) and antithrombotic (47%) drugs.

Cardiovascular abnormalities with normal blood pressure in tissue kallikrein-deficient mice

Tissue kallikrein is a serine protease thought to be involved in the generation of bioactive peptide kinins in many organs like the kidneys, colon, salivary glands, pancreas, and blood vessels. Low renal synthesis and urinary excretion of tissue kallikrein have been repeatedly linked to hypertension in animals and humans, but the exact role of the protease in cardiovascular function has not been established largely because of the lack of specific inhibitors. This study demonstrates that mice lacking tissue kallikrein are unable to generate significant levels of kinins in most tissues and develop cardiovascular abnormalities early in adulthood despite normal blood pressure. The heart exhibits septum and posterior wall thinning and a tendency to dilatation resulting in reduced left ventricular mass. Cardiac function estimated in vivo and in vitro is decreased both under basal conditions and in response to ��adrenergic stimulation. Furthermore, flow-induced vasodilatation is impaired in isolated perfused carotid arteries, which express, like the heart, low levels of the protease. These data show that tissue kallikrein is the main kinin-generating enzyme in vivo and that a functional kallikrein���kinin system is necessary for normal cardiac and arterial function in the mouse. They suggest that the kallikrein���kinin system could be involved in the development or progression of cardiovascular diseases.

Dieta e fatores de riscos metab��licos para doen��a cardiovascular em adultos e idosos residentes no munic��pio de S��o Paulo: uma an��lise por modelos de equa����es estruturais

Introdu����o: As doen��as cardiovasculares s��o a principal causa de morte no Brasil e no mundo e apresentam importante contribui����o para a carga global de doen��as. A dieta tem sido considerada um dos determinantes prim��rios do estado de sa��de dos indiv��duos, atuando na modula����o dos fatores de risco metab��licos para doen��a cardiovascular. Objetivos: Desenvolver um modelo conceitual para a rela����o entre fatores de risco metab��licos e investigar sua associa����o com padr��es de dieta de adultos e idosos residentes no munic��pio de S��o Paulo. M��todos: Estudo transversal de base populacional com amostra probabil��stica de adultos e idosos, residentes em ��rea urbana do munic��pio de S��o Paulo, que participaram do Inqu��rito de Sa��de do Munic��pio de S��o Paulo, realizado em duas fases entre os anos de 2008 e 2011 (estudo ISA Capital 2008). Na primeira fase do estudo, 1.102 adultos e idosos, de ambos os sexos, foram entrevistados no domic��lio, por meio da aplica����o de question��rio estruturado e do recordat��rio alimentar de 24 horas. Na segunda fase, 642 indiv��duos adultos e idosos foram reavaliados quanto ao consumo alimentar por meio da aplica����o, por telefone, do segundo recordat��rio alimentar, e, destes, 592 participaram da coleta domiciliar de amostras de sangue venoso, da medi����o antropom��trica e da aferi����o da press��o arterial por t��cnico de enfermagem. Os alimentos relatados em ambos os recordat��rios foram agrupados segundo a similaridade do valor nutricional e h��bitos alimentares da popula����o, e corrigidos pela vari��ncia intrapessoal da ingest��o por procedimentos estat��sticos da plataforma online Multiple Source Method. Os grupos de alimentos foram analisados por meio de an��lise fatorial explorat��ria e confirmat��ria (manuscrito 1) e por modelos de equa����es estruturais explorat��rios (manuscrito 3), a fim de obter os padr��es de dieta. O modelo conceitual da rela����o entre os fatores de risco metab��licos (leptina s��rica, prote��na C-reativa de alta sensibilidade s��rica, press��o arterial sist��lica e diast��lica, raz��o colesterol total/lipoprote��na de alta densidade, raz��o triacilglicerol/lipoprote��na de alta densidade, glicemia de jejum plasm��tica, circunfer��ncia da cintura e peso corporal) foi obtido por modelos de equa����es estruturais estratificados por sexo (manuscrito 2). Por fim, a associa����o dos padr��es de dieta com o modelo conceitual proposto (manuscrito 3) foi investigada por modelos de equa����es estruturais explorat��rios. ��ndices de qualidade de ajuste foram estimados para avaliar a adequa����o de todos os modelos. As an��lises foram realizadas no programa Mplus vers��o 6.12. Resultados: No manuscrito 1, a an��lise fatorial explorat��ria revelou a exist��ncia de dois padr��es de dieta, os quais apresentaram boa qualidade de ajuste na an��lise fatorial confirmat��ria quando aplicados os pontos de corte de cargas fatoriais |0,25| na rota����o obl��qua Promax. No manuscrito 2, a rela����o entre os fatores de risco metab��licos foi diferente entre os sexos. Nas mulheres, a leptina s��rica apresentou efeitos indiretos e positivos, mediados pelo peso corporal e pela circunfer��ncia da cintura, em todos os fatores de risco avaliados. J�� nos homens, a leptina s��rica apresentou efeitos diretos e positivos sobre a prote��na C-reativa de alta sensibilidade e efeitos indiretos e positivos (mediados pelo peso corporal e pela circunfer��ncia da cintura) sobre a raz��o triacilglicerol/lipoprote��na de alta densidade, colesterol total/lipoprote��na de alta densidade e glicemia de jejum plasm��tica. No manuscrito 3, foram obtidos tr��s padr��es de dieta, dos quais o Tradicional apresentou rela����o direta e negativa com a leptina s��rica e rela����o indireta e negativa com o peso corporal e a circunfer��ncia da cintura, bem como com os demais fatores de risco metab��licos. J�� o padr��o Prudente apresentou rela����o direta e negativa com a press��o arterial sist��lica, enquanto o padr��o Moderno n��o se associou aos fatores de risco metab��licos investigados. Conclus��o: Diferen��as nos padr��es de dieta de acordo com o tipo de rota����o fatorial empregada foram observadas. A rela����o entre os fatores de risco metab��licos para doen��a cardiovascular foi distinta entre homens e mulheres, sendo a leptina um dos poss��veis horm��nios envolvidos. Os padr��es de dieta Tradicional e Prudente associaram-se inversamente com os fatores de risco metab��licos, desempenhando uma importante estrat��gia de preven����o e controle ��s doen��as cardiovasculares no pa��s.

Risco cardiovascular e sua associa����o com vari��veis demogr��ficas, cl��nicas e psicossociais em pessoas vivendo com HIV/aids

Trata-se de um estudo anal��tico de corte transversal, que visa avaliar o risco cardiovascular de PVHA segundo o Escore de Framingham e identificar a associa����o entre o risco e as vari��veis demogr��ficas, comportamentais, psicossociais e cl��nicas de PVHA. O estudo foi aprovado na Secretaria Municipal de Sa��de e no Comit�� de ��tica da Escola de Enfermagem de Ribeir��o Preto, a coleta de dados foi realizada no per��odo de outubro de 2014 a agosto de 2015 em cinco Servi��os de Atendimento Especializado ��s PVHA utilizando question��rio sociodemogr��fico, cl��nico e comportamental, avalia����o da alimenta����o saud��vel, Invent��rio de Sintomas de Stress para Adultos de Lipp e avalia����o do risco cardiovascular por meio do Escore de Framingham. A an��lise dos dados ocorreu atrav��s de estat��stica descritiva e teste de associa����o entre as vari��veis, onde foi adotado n��vel de signific��ncia com valor de p<0,05. Identificou-se que 58,3% pertenciam ao sexo masculino, 69,1% apresentavam idade acima de 40 anos, com m��dia de 44,4 anos, 40,6% referiram ser brancos e 40,0% pardos, e 70,9% eram heterossexuais. Observou-se que 64,0% eram sedent��rios, 35,4% tabagistas e 40,0% faziam uso de bebida alc��olica regularmente. Do mesmo modo, 73,7% consideraram sua alimenta����o saud��vel, no entanto, ao ser avaliado de acordo com o escore da alimenta����o saud��vel, 70,9% obtiveram score intermedi��rio para alimenta����o. Com rela����o ��s vari��veis psicossociais, foi identificado que 52,0% tinham menos de oito anos de estudo, e 80,6% referiram receber at�� tr��s sal��rios m��nimos por m��s. Quanto aos sintomas de estresse, foi visto que 29,1% e 22,3% estavam nas fases de resist��ncia e exaust��o, respectivamente. Al��m disso, identificou-se que 15,4% da amostra tinha diagn��stico m��dico para depress��o e que 71,4% n��o realizavam atividades de lazer regularmente. Com rela����o ��s vari��veis cl��nicas gerais, 57,7% referiram antecedentes familiares para HAS, 40,6% para DM, 21,7% para IAM e 27,4% para AVE. Quanto aos antecedentes pessoais, foi visto que 15,4% eram hipertensos, 8,0% eram diab��ticos e 8,0% tinham dislipidemia. Desta mesma amostra, 45,2% apresentavam IMC maior que 25,0 kg/m�� e 41,7% estavam em s��ndrome metab��lica. Com rela����o ��s vari��veis cl��nicas relacionadas ao HIV, observou-se que 42,2% e 32,0% possu��am o diagn��stico de soropositividade e fazem uso de TARV h�� mais de dez anos, respectivamente. A contagem de c��lulas TCD4+ e carga viral mostrou que 82,8% dos participantes apresentaram contagem maior que 350 cels/mm��, e 80,6% tinham carga viral indetect��vel. Foi identificado que 25,8% dos sujeitos apresentam risco cardiovascular de m��dio a alto, segundo o Escore de Framingham. Apenas as vari��veis sociodemogr��ficas sexo (p=0,006), idade (p<0,001) e estado civil (p=0,003) apresentaram associa����o com o risco cardiovascular calculado pelo Escore de Framingham. Nas vari��veis comportamentais, as fases de estresse (p=0,039) tiveram associa����o com o risco cardiovascular, e com rela����o ��s vari��veis cl��nicas, antecedentes familiares para DM (p=0,035), HAS, DM e SM (p<0,001) e DLP (p=0,030) apresentaram signific��ncia estat��stica. Nas vari��veis cl��nicas relacionadas ao HIV, o tempo de diagn��stico (p=0,005) e o tempo de TARV (p=0,038) tamb��m apresentaram associa����o. Conclui-se que 25,8% de PVHA no munic��pio de Ribeir��o Preto apresentam risco cardiovascular de moderado a alto, medido pelo Escore de Framingham

Efeito da cirurgia bari��trica sobre par��metros cl��nicos, laboratoriais e fatores de risco cardiovascular

Introdu����o - Na preven����o prim��ria das doen��as cardiovasculares, a ado����o de estilo de vida saud��vel representa uma das estrat��gias mais importantes. Entretanto, baixos ��ndices de ades��o e o abandono da dieta constituem obst��culo importante ao tratamento. Neste sentido, as interven����es cir��rgicas surgiram como um mecanismo promotor da restri����o alimentar e t��m ganhado import��ncia n��o s�� pelo tratamento da obesidade como tamb��m no controle dos fatores de risco cardiovascular e na poss��vel redu����o da mortalidade. Atrav��s de estudos cl��nicos foi poss��vel observar que estas estrat��gias cir��rgicas promovem profundas modifica����es estruturais no trato gastrointestinal gerando aumento da saciedade e da sensibilidade �� insulina. Em especial para os pacientes diab��ticos, por si s�� associados a maior risco cardiovascular, as cirurgias bari��tricas seriam capazes de promover um efeito muito intenso e agudo sobre os marcadores relacionados ao desenvolvimento da aterosclerose. Um evento muito definido no tempo como uma interven����o cir��rgica pode ser muito ��til para o estudo e identifica����o de mecanismos que ainda n��o est��o completamente estabelecidos no processo ateroscler��tico. Objetivos - Analisar o comportamento das vari��veis laboratoriais, cl��nicas e estruturais relacionadas ao desenvolvimento e progress��o da aterosclerose em indiv��duos diab��ticos submetidos �� cirurgia bari��trica. M��todos - Foram inclu��dos vinte volunt��rios diab��ticos refrat��rios ao tratamento cl��nico e que apresentavam obesidade abdominal. Deste grupo, metade foi aleatoriamente selecionada para realiza����o da cirurgia bari��trica e metade foi mantida em tratamento cl��nico otimizado. Todos os participantes foram submetidos a exames cl��nicos e bioqu��micos nas mesmas ocasi��es, at�� trinta dias antes da cirurgia, tr��s e vinte e quatro meses ap��s a cirurgia. Nestas ocasi��es al��m do perfil lip��dico e da glicemia, determinamos os horm��nios incret��nicos, adipocinas. A avalia����o da quantidade de gordura epic��rdica e a presen��a de esteatose hep��tica ser�� realizada somente ap��s dois anos de seguimento em conjunto com as demais vari��veis,. Foram inclu��dos tamb��m 10 indiv��duos saud��veis e com IMC dentro da normalidade, como parte do grupo controle. Estes indiv��duos foram submetidos �� coleta de sangue em dois momentos para avalia����o dos mesmos metab��litos. Resultados - No momento pr��-interven����o os indiv��duos do grupo cir��rgico e clinico eram diferentes em rela����o ao IMC, Glicemia e Triglic��rides, sendo assim, os resultados obtidos foram ajustados minimizando o impacto destas diferen��as. Ap��s o seguimento de 3 meses, o grupo cir��rgico apresentou redu����o significativa nos valores de peso, IMC (33,4 �� 2,6 vs. 27,4��2,8 kg/m2, p < 0,001), HbA1c (9,26 �� 2,12 vs. 6,18��0,63%, p < 0,001), CT (182,9 �� 45,4 vs. 139,8 �� 13 mg/dl, p < 0,001), HDL (33,1 �� 7,7 vs. 38,4 �� 10,6 mg/dL, p < 0,001), TG (369,5 �� 324,6 vs. 130,8 �� 43,1 mg/dL, p < 0,001), Pro-insulina (12.72��9,11 vs. 1,76��1,14 pM, p < 0,001), RBP-4 (9,85��2,53 vs. 7,3��1,35 ng/ml, p < 0,001) e CCK (84,8��33,2 vs. 79,9 �� 31,1, ng/ml, p < 0,001), houve tamb��m aumento significativo nos n��veis de HDL-colesterol (33,1 �� 7,7 vs. 38,4 �� 10,6 mg/dL, p < 0,001), Glucagon (7,4 �� 7,9 vs. 10,2��9,7 pg/ml, p < 0,001) e FGF- 19 (74,1 �� 45,8 vs. 237,3 �� 234 pg/ml, p=0,001). Um dado interessante foi que os valores de Pro-insulina, RBP-4, HbA1c e HDL- colesterol no grupo cir��rgico atingiram valores similares ��queles do grupo controle tr��s meses ap��s a interven����o, sendo que o FGF-19 apresentava valor duas vezes maior do que o encontrado no grupo de indiv��duos saud��veis (237 �� 234 vs. 98 �� 102,1 pg/ml). O grupo cl��nico n��o apresentou varia����o nas vari��veis clinicas, apenas nos valores de glucagon com redu����o significativa no per��odo p��s-interven����o (18,1 �� 20,7 vs. 16,8 �� 18,4 pg/ml, p < 0,001). Conclus��o - Conclu��mos que indiv��duos diab��ticos descompensados e refrat��rios ao tratamento cl��nico, quando submetidos �� cirurgia bari��trica, apresentam uma altera����o profunda do ponto de vista cl��nico, metab��lico e hormonal, em rela����o ao indiv��duos de mesmo perfil mantidos em tratamento cl��nico otimizado. Esta importante altera����o, observada j�� com tr��s meses ap��s a interven����o, pode representar uma importante redu����o do risco cardiovascular nestes indiv��duos. Individualmente, a not��vel modifica����o dos valores de FGF-19 associadas �� interven����o devem ser estudadas com maior profundidade para compreens��o de seu significado e sua potencial utilidade como marcador ou como um dos protagonistas no mecanismo de preven����o cardiovascular

Efeito dos ��cidos graxos ��mega-3, ��mega-6 e ��mega-9 sobre o risco cardiovascular de indiv��duos adultos: estudo cl��nico de preven����o prim��ria.

INTRODU����O: As doen��as cardiovasculares (DCV) s��o a principal causa de morte no mundo, sendo muitos dos fatores de risco pass��veis de preven����o e controle. Embora as DCV sejam complexas em sua etiologia e desenvolvimento, a concentra����o elevada de LDL-c e baixa de HDL-c constituem os fatores de risco modific��veis mais monitorados na pr��tica cl��nica, embora n��o sejam capazes de explicar todos os eventos cardiovasculares. Portanto, investigar como interven����es farmacol��gicas e nutricionais podem modular par��metros oxidativos, f��sicos e estruturais das lipoprote��nas pode fornecer estimativa adicional ao risco cardiovascular. Dentre os diversos nutrientes e compostos bioativos relacionados ��s DCV, os lip��deos representam os mais investigados e descritos na literatura. Nesse contexto, os ��cidos graxos insaturados (��mega-3, ��mega-6 e ��mega-9) t��m sido foco de in��meros estudos. OBJETIVOS: Avaliar o efeito da suplementa����o com ��mega-3, ��mega-6 e ��mega-9 sobre os par��metros cardiometab��licos em indiv��duos adultos com m��ltiplos fatores de risco e sem evento cardiovascular pr��vio. MATERIAL E M��TODOS: Estudo cl��nico, randomizado, duplo-cego, baseado em interven����o nutricional (3,0 g/dia de ��cidos graxos) sob a f��rmula de c��psulas contendo: ��mega-3 (37 por cento de EPA e 23 por cento de DHA) ou ��mega-6 (65 por cento de ��cido linoleico) ou ��mega-9 (72 por cento de ��cido oleico). A amostra foi composta por indiv��duos de ambos os sexos, com idade entre 30 e 74 anos, apresentando pelo menos um dos seguintes fatores de risco: Dislipidemia, Diabetes Mellitus, Obesidade e Hipertens��o Arterial Sist��mica. Ap��s aprova����o do Comit�� de ��tica, os indiv��duos foram distribu��dos nos tr��s grupos de interven����o. No momento basal, os indiv��duos foram caracterizados quanto aos aspectos demogr��ficos (sexo, idade e etnia) e cl��nicos (medicamentos, doen��as atuais e antecedentes familiares). Nos momentos basal e ap��s 8 semanas de interven����o, amostras de sangue foram coletadas ap��s 12h de jejum. A partir do plasma foram analisados: perfil lip��dico (CT, LDL-c, HDL-c, TG), apolipoprote��nas AI e B, ��cidos graxos n��o esterificados, atividade da PON1, LDL(-) e auto-anticorpos, ��cidos graxos, glicose, insulina, tamanho e distribui����o percentual da LDL (7 subfra����es e fen��tipo A e n��o-A) e HDL (10 subfra����es). O efeito do tempo, da interven����o e associa����es entre os ��cidos graxos e aspectos qualitativos das lipoprote��nas foram testados (SPSS vers��o 20.0, p <0,05). RESULTADOS: Uma primeira an��lise dos resultados baseada em um corte transversal demonstrou, por meio da an��lise de tend��ncia linear ajustada pelo n��vel de risco cardiovascular, que o maior tercil plasm��tico de DHA se associou positivamente com HDL-c, HDLGRANDE e tamanho de LDL e negativamente com HDLPEQUENA e TG. Observou-se tamb��m que o maior tercil plasm��tico de ��cido linoleico se associou positivamente com HDLGRANDE e tamanho de LDL e negativamente com HDLPEQUENA e TG. Esse perfil de associa����o n��o foi observado quando foram avaliados os par��metros diet��ticos. Avaliando uma subamostra que incluiu indiv��duos tabagistas suplementados com ��mega-6 e ��mega-3, observou-se que ��mega-3 modificou positivamente o perfil lip��dico e as subfra����es da HDL. Nos modelos de regress��o linear ajustados pela idade, sexo e hipertens��o, o DHA plasm��tico apresentou associa����es negativas com a HDLPEQUENA. Quando se avaliou exclusivamente o efeito do ��mega-3 em indiv��duos tabagistas e n��o tabagistas, observou-se que fumantes, do sexo masculino, acima de 60 anos de idade, apresentando baixo percentual plasm��tico de EPA e DHA (<8 por cento ), com excesso de peso e gordura corporal elevada, apresentam maior probabilidade de ter um perfil de subfra����es de HDL mais aterog��nicas. Tendo por base os resultados acima, foi comparado o efeito do ��mega-3, ��mega-6 e ��mega-9 sobre os par��metros cardiometab��licos. O ��mega-3 promoveu redu����o no TG, aumento do percentual de HDLGRANDE e redu����o de HDLPEQUENA. O papel cardioprotetor do ��mega-3 foi refor��ado pelo aumento na incorpora����o de EPA e DHA, no qual indiv��duos com EPA e DHA acima de 8 por cento apresentaram maior probabilidade de ter HDLGRANDE e menor de ter HDLPEQUENA. Em adi����o, observou-se tamb��m que o elevado percentual plasm��tico de ��mega-9 se associou com part��culas de LDL menos aterog��nicas (fen��tipo A). CONCLUS��O: ��cidos graxos plasm��ticos, mas n��o diet��ticos, se correlacionam com par��metros cardiometab��licos. A suplementa����o com ��mega-3, presente no ��leo de peixe, promoveu redu����o no TG e melhoria nos par��metros qualitativos da HDL (mais HDLGRANDE e menos HDLPEQUENA). Os benef��cios do ��mega-3 foram particularmente relevantes nos indiv��duos tabagistas e naqueles com menor conte��do basal de EPA e DHA plasm��ticos. Observou-se ainda que o ��mega-9 plasm��tico, presente no azeite de oliva, exerceu impacto positivo no tamanho e subfra����es da LDL.