Validation of a generalized transfer function to noninvasively derive central blood pressure during exercise

Exercise brachial blood pressure ( BP) predicts mortality, but because of wave reflection, central ( ascending aortic) pressure differs from brachial pressure. Exercise central BP may be clinically important, and a noninvasive means to derive it would be useful. The purpose of this study was to test the validity of a noninvasive technique to derive exercise central BP. Ascending aortic pressure waveforms were recorded using a micromanometer-tipped 6F Millar catheter in 30 patients (56 +/- 9 years; 21 men) undergoing diagnostic coronary angiography. Simultaneous recordings of the derived central pressure waveform were acquired using servocontrolled radial tonometry at rest and during supine cycling. Pulse wave analysis of the direct and derived pressure signals was performed offline (SphygmoCor 7.01). From rest to exercise, mean arterial pressure and heart rate were increased by 20 +/- 10 mm Hg and 15 +/- 7 bpm, respectively, and central systolic BP ranged from 77 to 229 mm Hg. There was good agreement and high correlation between invasive and noninvasive techniques with a mean difference (+/- SD) for central systolic BP of -1.3 +/- 3.2 mm Hg at rest and -4.7 +/- 3.3 mm Hg at peak exercise ( for both r=0.995; P < 0.001). Conversely, systolic BP was significantly higher peripherally than centrally at rest (155 +/- 33 versus 138 +/- 32mm Hg; mean difference, -16.3 +/- 9.4mm Hg) and during exercise (180 +/- 34 versus 164 +/- 33 mm Hg; mean difference, -15.5 +/- 10.4 mm Hg; for both P < 0.001). True myocardial afterload is not reliably estimated by peripheral systolic BP. Radial tonometry and pulse wave analysis is an accurate technique for the noninvasive determination of central BP at rest and during exercise.

Brachial blood pressure but not carotid arterial waveforms predict cardiovascular events in elderly female hypertensives

Central arterial waveforms and related indices of large artery properties can be determined with relative ease. This would make them an attractive adjunct in the risk stratification for cardiovascular disease. Although they have been associated with some classical risk factors and the presence of coronary disease, their prospective value in predicting cardiovascular outcomes is unknown. The present study determined the relative predictive value for cardiovascular disease-free survival of large artery properties as compared with noninvasive brachial blood pressure alone in a population of elderly female hypertensive subjects. We measured systemic arterial compliance, central systolic pressure, and carotid augmentation index in a subset of female participants in the Second Australian National Blood Pressure Study ( untreated blood pressure 169/88 +/- 12/ 8 mm Hg). There were a total of 53 defined events during a median of 4.1 years of follow-up in 484 women with complete measurements. Although baseline blood pressures at the brachial artery predicted cardiovascular disease-free survival ( hazard ratio [HR], 2.3; 95% CI, 1.3 to 4.1 for pulse pressure >= 81 versus < 81 mm Hg; P = 0.01), no such relation was found for carotid augmentation index ( HR, 0.80; 95% CI, 0.44 to 1.44; P value not significant) or systemic arterial compliance ( HR, 1.25; 95% CI, 0.72 to 2.16; P value not significant). Blood pressure, but not noninvasively measured central arterial waveforms, predict outcome in the older female hypertensive patient. Thus, blood pressure measurement alone is superior to measurement of arterial waveforms in predicting outcome in this group.

Relations between physiologic parameters and pulse transit time during loaded breathing

Pulse transit time (PTT) is a non-invasive measure, defined as time taken for the pulse pressure waves to travel from the R-wave of electrocardiogram to a selected peripheral site. Baseline PTT value is known to be influenced by physiologic variables like heart rate (HR), blood pressure (BP) and arterial compliance (AC). However, few quantitative data are available describing the factors which can influence PTT measurements in a child during breathing. The aim of this study was to investigate the effects of changes in breathing efforts on PTT baseline and fluctuations. Two different inspiratory resistive loading (IRL) devices were used to simulate loaded breathing in order to induce these effects. It is known that HR can influence the normative PTT value however the effect of HR variability (HRV) is not well-studied. Two groups of 3 healthy children ( 0.05) HR changes during all test activities. Results showed that HRV is not the sole contributor to PTT variations and suggest that changes in other physiologic parameters are also equally important. Hence, monitoring PTT measurement can be indicative of these associated changes during tidal or increased breathing efforts in healthy children.

Epidemiology and genetic architecture of blood pressure: a family based study of Generation Scotland

Hypertension is a major risk factor for cardiovascular disease and mortality, and a growing global public health concern, with up to one-third of the world’s population affected. Despite the vast amount of evidence for the benefits of blood pressure (BP) lowering accumulated to date, elevated BP is still the leading risk factor for disease and disability worldwide. It is well established that hypertension and BP are common complex traits, where multiple genetic and environmental factors contribute to BP variation. Furthermore, family and twin studies confirmed the genetic component of BP, with a heritability estimate in the range of 30-50%. Contemporary genomic tools enabling the genotyping of millions of genetic variants across the human genome in an efficient, reliable, and cost-effective manner, has transformed hypertension genetics research. This is accompanied by the presence of international consortia that have offered unprecedentedly large sample sizes for genome-wide association studies (GWASs). While GWAS for hypertension and BP have identified more than 60 loci, variants in these loci are associated with modest effects on BP and in aggregate can explain less than 3% of the variance in BP. The aims of this thesis are to study the genetic and environmental factors that influence BP and hypertension traits in the Scottish population, by performing several genetic epidemiological analyses. In the first part of this thesis, it aims to study the burden of hypertension in the Scottish population, along with assessing the familial aggregation and heritialbity of BP and hypertension traits. In the second part, it aims to validate the association of common SNPs reported in the large GWAS and to estimate the variance explained by these variants. In this thesis, comprehensive genetic epidemiology analyses were performed on Generation Scotland: Scottish Family Health Study (GS:SFHS), one of the largest population-based family design studies. The availability of clinical, biological samples, self-reported information, and medical records for study participants has allowed several assessments to be performed to evaluate factors that influence BP variation in the Scottish population. Of the 20,753 subjects genotyped in the study, a total of 18,470 individuals (grouped into 7,025 extended families) passed the stringent quality control (QC) criteria and were available for all subsequent analysis. Based on the BP-lowering treatment exposure sources, subjects were further classified into two groups. First, subjects with both a self-reported medications (SRMs) history and electronic-prescription records (EPRs; n =12,347); second, all the subjects with at least one medication history source (n =18,470). In the first group, the analysis showed a good concordance between SRMs and EPRs (kappa =71%), indicating that SRMs can be used as a surrogate to assess the exposure to BP-lowering medication in GS:SFHS participants. Although both sources suffer from some limitations, SRMs can be considered the best available source to estimate the drug exposure history in those without EPRs. The prevalence of hypertension was 40.8% with higher prevalence in men (46.3%) compared to women (35.8%). The prevalence of awareness, treatment and controlled hypertension as defined by the study definition were 25.3%, 31.2%, and 54.3%, respectively. These findings are lower than similar reported studies in other populations, with the exception of controlled hypertension prevalence, which can be considered better than other populations. Odds of hypertension were higher in men, obese or overweight individuals, people with a parental history of hypertension, and those living in the most deprived area of Scotland. On the other hand, deprivation was associated with higher odds of treatment, awareness and controlled hypertension, suggesting that people living in the most deprived area may have been receiving better quality of care, or have higher comorbidity levels requiring greater engagement with doctors. These findings highlight the need for further work to improve hypertension management in Scotland. The family design of GS:SFHS has allowed family-based analysis to be performed to assess the familial aggregation and heritability of BP and hypertension traits. The familial correlation of BP traits ranged from 0.07 to 0.20, and from 0.18 to 0.34 for parent-offspring pairs and sibling pairs, respectively. A higher correlation of BP traits was observed among first-degree relatives than other types of relative pairs. A variance-component model that was adjusted for sex, body mass index (BMI), age, and age-squared was used to estimate heritability of BP traits, which ranged from 24% to 32% with pulse pressure (PP) having the lowest estimates. The genetic correlation between BP traits showed a high correlation between systolic (SBP), diastolic (DBP) and mean arterial pressure (MAP) (G: 81% to 94%), but lower correlations with PP (G: 22% to 78%). The sibling recurrence risk ratio (λS) for hypertension and treatment were calculated as 1.60 and 2.04 respectively. These findings confirm the genetic components of BP traits in GS:SFHS, and justify further work to investigate genetic determinants of BP. Genetic variants reported in the recent large GWAS of BP traits were selected for genotyping in GS:SFHS using a custom designed TaqMan® OpenArray®. The genotyping plate included 44 single nucleotide polymorphisms (SNPs) that have been previously reported to be associated with BP or hypertension at genome-wide significance level. A linear mixed model that is adjusted for age, age-squared, sex, and BMI was used to test for the association between the genetic variants and BP traits. Of the 43 variants that passed the QC, 11 variants showed statistically significant association with at least one BP trait. The phenotypic variance explained by these variant for the four BP traits were 1.4%, 1.5%, 1.6%, and 0.8% for SBP, DBP, MAP, and PP, respectively. The association of genetic risk score (GRS) that were constructed from selected variants has showed a positive association with BP level and hypertension prevalence, with an average effect of one mmHg increase with each 0.80 unit increases in the GRS across the different BP traits. The impact of BP-lowering medication on the genetic association study for BP traits has been established, with typical practice of adding a fixed value (i.e. 15/10 mmHg) to the measured BP values to adjust for BP treatment. Using the subset of participants with the two treatment exposure sources (i.e. SRMs and EPRs), the influence of using either source to justify the addition of fixed values in SNP association signal was analysed. BP phenotypes derived from EPRs were considered the true phenotypes, and those derived from SRMs were considered less accurate, with some phenotypic noise. Comparing SNPs association signals between the four BP traits in the two model derived from the different adjustments showed that MAP was the least impacted by the phenotypic noise. This was suggested by identifying the same overlapped significant SNPs for the two models in the case of MAP, while other BP traits had some discrepancy between the two sources

Effect of telmisartan on functional outcome, recurrence, and blood pressure in patients with acute mild ischemic stroke: a PRoFESS subgroup analysis

Background and Purpose—High blood pressure (BP) is common in acute ischemic stroke and associated independently with a poor functional outcome. However, the management of BP acutely remains unclear because no large trials have been completed. Methods—The factorial PRoFESS secondary stroke prevention trial assessed BP-lowering and antiplatelet strategies in 20 332 patients; 1360 were enrolled within 72 hours of ischemic stroke, with telmisartan (angiotensin receptor antagonist, 80 mg/d, n647) vs placebo (n713). For this nonprespecified subgroup analysis, the primary outcome was functional outcome at 30 days; secondary outcomes included death, recurrence, and hemodynamic measures at up to 90 days. Analyses were adjusted for baseline prognostic variables and antiplatelet assignment. Results—Patients were representative of the whole trial (age 67 years, male 65%, baseline BP 147/84 mm Hg, small artery disease 60%, NIHSS 3) and baseline variables were similar between treatment groups. The mean time from stroke to recruitment was 58 hours. Combined death or dependency (modified Rankin scale: OR, 1.03; 95% CI, 0.84–1.26; P0.81; death: OR, 1.05; 95% CI, 0.27–4.04; and stroke recurrence: OR, 1.40; 95% CI, 0.68–2.89; P0.36) did not differ between the treatment groups. In comparison with placebo, telmisartan lowered BP (141/82 vs 135/78 mmHg, difference 6 to 7 mmHg and 2 to 4 mmHg; P0.001), pulse pressure (3 to 4 mmHg; P0.002), and rate-pressure product (466 mmHg.bpm; P0.0004). Conclusion—Treatment with telmisartan in 1360 patients with acute mild ischemic stroke and mildly elevated BP appeared to be safe with no excess in adverse events, was not associated with a significant effect on functional dependency, death, or recurrence, and modestly lowered BP.

No effect of multivitamin supplementation on central blood pressure in healthy older people: a randomized controlled trial

BACKGROUND AND AIMS: Central blood pressure rises with age, which increases cardiovascular risk. There is some evidence that nutritional supplements may be useful to reduce central blood pressures in older people, but no studies have investigated the effects of multivitamin supplements for this purpose. This randomized, double-blind, placebo-controlled study investigated the effects of 16-weeks supplementation with gender-specific multivitamin and herbal supplements.

METHOD: Participants were healthy individuals, free from heart disease, and included 160 females aged ≥ 50 and 79 males aged 50-65 years. Analyses of co-variance, correcting for baseline cardiovascular assessments, were used to determine the effects of supplementation on central cardiovascular measures including augmentation index, augmentation pressure and pulse pressure. Significance was set at p = 0.016.

RESULTS: No effects of multivitamin supplementation were observed in either males or females (respectively) for central augmentation index (p = 0.841; p = 0.296), central augmentation pressure (p = 0.794; p = 0.442), and central pulse pressure (p = 0.078; p = 0.304). Similarly, there was no treatment effect observed for brachial systolic, diastolic or pulse pressures.

CONCLUSION: Four months multivitamin supplementation does not appear to exert any benefit to measures of central blood pressure in healthy older people.

L’évaluation des déterminants des paramètres hémodynamiques centraux à l’aide de la cohorte populationnelle CARTaGENE.

Les maladies cardiovasculaires ont un impact considérable sur la vie des Canadiens, et de nombreux efforts ont permis d’identifier différents facteurs de risque associés à cette condition. L’hypertension artérielle représente un de ces facteurs modifiables les plus importants. Quoique l’hypertension est définie à l’aide de mesures de pression artérielle en périphérie, il devient de plus en plus apparent que la mesure de pression centrale et de ses composantes auraient des avantages au niveau de la prédiction de la survenue d’événements cardiovasculaires. Le présent mémoire vise à mieux caractériser deux déterminants de cette pression centrale, le traitement antihypertenseur à base de bêtabloqueurs et l’insuffisance rénale chronique précoce. En utilisant les données recueillies dans la banque de données populationnelle CARTaGENE, il a été possible à l’aide d’analyses statistiques par appariement basé sur le coefficient de propension de démontrer que l’utilisation d’agents antihypertensifs de type bêtabloqueurs était associée à un profil hémodynamique central défavorable. Ainsi, les individus recevant ces agents avaient une pression centrale et une amplification artérielle plus élevées que des individus du groupe contrôle apparié et ce, malgré une pression périphérique identique. Cet effet semblait être incomplètement expliqué par la réduction du rythme cardiaque associé à l’utilisation de bêtabloqueurs. Aussi, il a été démontré que l’insuffisance rénale chronique de stade 3 (débit de filtration glomérulaire estimé entre 30 et 60 mL/min/1.73m2) n’était pas associée à une élévation des paramètres hémodynamiques centraux, contrairement à ce qui avait déjà été décrit chez des individus avec insuffisance rénale chronique plus avancée. De plus, le niveau d’albuminurie ne serait également pas associé à un changement du profil central dans un sous-groupe de la cohorte CARTaGENE.

L’évaluation des déterminants des paramètres hémodynamiques centraux à l’aide de la cohorte populationnelle CARTaGENE

Les maladies cardiovasculaires ont un impact considérable sur la vie des Canadiens, et de nombreux efforts ont permis d’identifier différents facteurs de risque associés à cette condition. L’hypertension artérielle représente un de ces facteurs modifiables les plus importants. Quoique l’hypertension est définie à l’aide de mesures de pression artérielle en périphérie, il devient de plus en plus apparent que la mesure de pression centrale et de ses composantes auraient des avantages au niveau de la prédiction de la survenue d’événements cardiovasculaires. Le présent mémoire vise à mieux caractériser deux déterminants de cette pression centrale, le traitement antihypertenseur à base de bêtabloqueurs et l’insuffisance rénale chronique précoce. En utilisant les données recueillies dans la banque de données populationnelle CARTaGENE, il a été possible à l’aide d’analyses statistiques par appariement basé sur le coefficient de propension de démontrer que l’utilisation d’agents antihypertensifs de type bêtabloqueurs était associée à un profil hémodynamique central défavorable. Ainsi, les individus recevant ces agents avaient une pression centrale et une amplification artérielle plus élevées que des individus du groupe contrôle apparié et ce, malgré une pression périphérique identique. Cet effet semblait être incomplètement expliqué par la réduction du rythme cardiaque associé à l’utilisation de bêtabloqueurs. Aussi, il a été démontré que l’insuffisance rénale chronique de stade 3 (débit de filtration glomérulaire estimé entre 30 et 60 mL/min/1.73m2) n’était pas associée à une élévation des paramètres hémodynamiques centraux, contrairement à ce qui avait déjà été décrit chez des individus avec insuffisance rénale chronique plus avancée. De plus, le niveau d’albuminurie ne serait également pas associé à un changement du profil central dans un sous-groupe de la cohorte CARTaGENE.

Arterial stiffness and cardiovascular risk factors

Background: As the human body ages, the arteries gradually lose their elasticity and become stiffer. Although inevitable, this process is influenced by hereditary and environmental factors. Interestingly, many classic cardiovascular risk factors affect the arterial stiffness. During the last decade, accelerated arterial stiffening has been recognized as an important cardiovascular risk factor associated with increased mortality as well as with several chronic disorders. Objectives: This thesis examines the role of arterial stiffness in relation to variations in a physiological feature in healthy individuals. In addition, the effect on arterial stiffness of an acute transitory disease and the effect of a chronic disease are studied. Furthermore, the thesis analyzes the prognostic value of a marker of arterial stiffness in individuals with chronic disease. Finally, a potential method of reducing arterial stiffness is evaluated. Material and study design: The first study examines pulse wave reflection and pulse wave velocity in relation to muscle fibre distribution in healthy middle-aged men. In the second study, pulse wave reflection in women with current or previous preeclampsia is compared to a healthy control group. The effect of aging on the different blood pressure indices in patients with type 1 diabetes is examined in the third study, whereas the fourth paper studies the relation between these blood pressure indices and mortality in type 2 diabetes. The fifth study evaluates how intake of a fermented milk product containing bioactive peptides affects pulse wave reflection in individuals with mild hypertension. Results and conclusions: Muscle fibre type distribution is not an independent determinant of arterial stiffness in middle-aged males. Pulse wave reflection is increased in pregnant women with preeclampsia, but not in previously preeclamptic non-pregnant women. Patients with type 1 diabetes have a higher and more rapidly increasing pulse pressure, which suggests accelerated arterial stiffening. In elderly type 2 diabetic patients, very high and very low levels of pulse pressure are associated with higher mortality. Intake of milk-derived bioactive peptides reduces pulse wave reflection in hypertensive males but not in hypertensive females.

Fatores associados à redução do índice tornozelo-braquial aferido por dois métodos diferentes em idosos hipertensos independentes para as atividades de vida diária

Nos últimos anos, a população de idosos vem crescendo em todo o mundo, e a pesquisa de marcadores de risco cardiovascular mais precoces é de fundamental importância. Um desses marcadores é a doença arterial periférica (DAP), cuja prevalência aumenta com a idade. A DAP pode ser avaliada de forma simples e não invasiva através do índice tornozelo-braquial (ITB) que, por sua vez, pode ser obtido por cálculos diferentes. Até o momento, apenas o método tradicional foi utilizado no cálculo do ITB na população idosa. O objetivo do presente estudo foi avaliar, em idosos hipertensos que se mostrassem independentes para as atividades diárias, os principais fatores relacionados à redução do ITB, considerando-se duas formas distintas de calcular o índice. Os pacientes (n=65) foram submetidos à avaliação clínica, geriátrica e laboratorial, e divididos nos grupos com ITB normal (> 0,9) e ITB reduzido (≤ 0,9). Inicialmente o ITB foi calculado a partir da divisão da maior pressão sistólica dos membros inferiores pela maior pressão das artérias braquiais. Em seguida, o cálculo do ITB foi realizado por um método alternativo, a partir da utilização da menor ao invés da maior média de pressão sistólica nos membros inferiores. A média de idade foi de 74 anos, sendo 76% do sexo feminino. A prevalência de ITB reduzido foi de 18% pelo método convencional e de 32% pelo método alternativo. Na avaliação pelo método convencional, o grupo com ITB baixo apresentou maior prevalência de doenças cardiovasculares (58 vs 9%, p<0,001), diabetes (83 vs 13%, p<0,01), síndrome metabólica (75 vs 41%, p<0,05), e valores significativamente maiores de pressão arterial sistólica (1699 vs 1523 mmHg, p<0,05) e pressão de pulso (877 vs 672 mmHg, p<0,01). A redução do ITB pelo método alternativo mostrou associação com as mesmas variáveis, mas adicionalmente com maior freqüência de tabagistas (29 vs 20%, p<0,05) e maiores níveis de LDL-colesterol (15413 vs 1245 mg/dl, p<0,05). Além disso, o método alternativo foi capaz de detectar pacientes sem alto risco pelo escore de Framingham, mas obesos e com síndrome metabólica. Esses dados apontariam para um valor adicional desta forma de estimar o risco ao escore de Framingham na estratificação de risco cardiovascular, sugerindo sua incorporação na rotina de avaliação de pacientes idosos

Avaliação de fatores de risco relacionados com aterosclerose subclínica em mulheres hipertensas

A aterosclerose e suas complicações são a principal causa de morbidade e mortalidade no mundo ocidental. O aumento da espessura da camada médio-intimal da carótida está associado com risco para doenças cardiovasculares, pois representa um marcador de aterosclerose subclínica, podendo ser detectada precocemente em indivíduos assintomáticos. O objetivo desse estudo foi identificar variáveis clínicas e nutricionais associadas com a aterosclerose subclínica em mulheres hipertensas. Estudo transversal envolvendo uma amostra de conveniência composta por 116 mulheres hipertensas entre 40 e 65 anos. Dados clínicos, como pressão arterial (PA) sistólica e diastólica, história de tabagismo, atividade física, uso de medicamentos foram coletados; foi feita a análise do perfil lipídico, glicemia e proteína C reativa (PCR); a avaliação dietética obtida pelo Recordatório de 24 horas e pelo Registro de três dias. A espessura médio-intimal (EMI) de carótidas foi realizada pelo aparelho de ultrassonografia. As pacientes foram divididas em dois grupos, de acordo com os valores da espessura médio-intimal de carótidas: EMI 0,9mm ou EMI > 0,9mm. Houve diferença significativa entre os grupos em relação à idade (50,846,62 vs 53,547,13; p=0,044), PA sistólica (134,5216,54 vs 142,9821,47; p=0,020), pressão de pulso (PP) (49,3611,03 vs 60,15 17,77; p<0,001), HDL (48,988,54 vs 44,057,45; p=0,004) e PCR (2,311,21 vs 3,051,34; p=0,016). Não houve diferença significativa em relação aos parâmetros antropométricos, exceto em relação à reactância (65,199,69 vs 61,447,88; p=0,036), avaliada pela bioimpedância elétrica (BIA). Quanto ao padrão de consumo alimentar, somente o consumo de gordura monoinsaturada foi diferente entre os grupos, sendo o maior consumo no grupo com menor valor de EMI (7,882,09 vs 7,022,06; p=0,031). Não houve diferença em relação à frequência de tabagismo e atividade física. Quando foi feita a análise de correlação da amostra, foi encontrada uma correlação entre a EMI de carótidas e idade (r=0,25; p=0,0067), PAS (r=0,19; p=0,0086); PP (r=0,30; p=0,0009), LDL (r=0,19; p=0,0434), assim como com gordura monoinsaturada (r= -0,25; p=0,0087), PCR (r=0,31; p=0,007) e HDL (r=-0,33; p=0,0004), porém apenas as variáveis HDL, PCRus e pressão de pulso mostraram ser preditoras independentes da EMI de carótida após feita uma análise de regressão linear multivariada. A proteína C reativa, HDL colesterol e pressão de pulso são importantes preditores independentes de aterosclerose subclínica.

O efeito agudo do chocolate amargo sob a função endotelial é dependente da idade em hipertensos com baixo risco cardiovascular

Dados recentes indicam uma relação inversa entre doença cardiovascular e consumo de flavonóides. O objetivo do estudo foi identificar parâmetros clínicos e vasculares de pacientes hipertensos tratados que apresentaram efeitos benéficos na função vascular após o consumo de chocolate amargo com 70% de cacau por sete dias. Vinte e um pacientes hipertensos em tratamento medicamentoso, ambos os sexos, com idades entre 40-65 anos, foram incluídos em um ensaio clínico intervencional com aferição de pressão arterial, dilatação mediada por fluxo braquial (DMF), tonometria arterial periférica (EndoPAT) e parâmetros hemodinâmicos centrais pelo SphygmoCor. Após sete dias de consumo de chocolate amargo (70% cacau) 75g/dia, as avaliações clínica e vascular foram repetidas. Os pacientes foram divididos em dois grupos de acordo com a resposta da DMF em respondedores (que apresentaram melhora na DMF, n= 12) e não-respondedores (que não apresentaram melhora, n = 9). O grupo respondedor apresentou menor média de idade (54 7 vs 61 6 anos, p = 0,037) e menor risco cardiovascular pelo escore de Framingham (2,5 1,8 vs 8,1 5,1%, p = 0,017). Além disso, os pacientes respondedores apresentaram valores mais baixos de pressão de pulso tanto periférica (55 9 vs 63 5 mmHg, p = 0,041), quanto central (44 10 vs 54 6, p = 0,021) quando comparado ao grupo não respondedor. A resposta da DMF apresentou correlação moderada e negativa com o escore de Framingham (r = -0,60, p = 0,014), com a DMF basal (r = 0,54, p = 0,011), com o índice de hiperemia reativa basal (IHR) obtido pelo EndoPAT (r = -0,56, p = 0,008) e com a pressão de pulso central (r = -0,43, p = 0,05). No entanto, após análise de regressão linear, apenas o escore de Framingham e o IHR basal foram associados com a resposta da DMF. Em conclusão, nesta amostra de pacientes hipertensos tratados, os indivíduos que apresentaram melhora da função endotelial com o consumo de chocolate amargo com 70% de cacau também mostraram redução da pressão arterial tanto sistólica como diastólica, eram mais jovens e tinham menor pressão de pulso e menor risco cardiovascular, apesar de uma disfunção endotelial basal

Impaired endothelium-dependent vasodilatation is a novel predictor of mortality in intensive care

Objective: Endothelial function may be impaired in critical illness. We hypothesized that impaired endothelium-dependent vasodilatation is a predictor of mortality in critically ill patients.
Design: Prospective observational cohort study.
Setting: Seventeen-bed adult intensive care unit in a tertiary referral university teaching hospital. Patients: Patients were recruited within 24 hrs of admission to the intensive care unit.
Interventions: The SphygmoCor Mx system was used to derive the aortic augmentation index from radial artery pulse pressure waveforms. Endothelium-dependent vasodilatation was calculated as the change in augmentation index in response to an endothelium-dependent vasodilator (salbutamol).
Measurements and Main Results: Demographics, severity of illness scores, and physiological parameters were collected. Statistically significant predictors of mortality identified using single regressor analysis were entered into a multiple logistic regression model. Receiver operator characteristic curves were generated. Ninety-four patients completed the study. There were 80 survivors and 14 nonsurvivors. The Simplified Acute Physiology Score II, the Sequential Organ Failure Assessment score, leukocyte count, and endothelium-dependent vasodilatation conferred an increased risk of mortality. In logistic regression analysis, endothelium-dependent vasodilatation was the only predictor of mortality with an adjusted odds ratio of 26.1 (95% confidence interval [CI], 4.3-159.5). An endothelium-dependent vasodilatation value of 0.5% or less predicted intensive care unit mortality with a sensitivity of 79% (CI, 59-88%) and specificity of 98% (CI, 94-99%).
Conclusions: In vivo bedside assessment of endothelium-dependent vasodilatation is an independent predictor of mortality in the critically ill. We have shown it to be superior to other validated severity of illness scores with high sensitivity and specificity.

Valor prognóstico cardiovascular da MAPA numa população hipertensa portuguesa

Efectuou-se um estudo prospectivo e observacional em 1200 doentes, maiores de 18 anos, com hipertensão essencial e sem eventos cardiovasculares (CV) prévbs que foram referenciados entre 1991 e 1998 para realização de MAPA no Serviço de Cardiologia do Hospital Infante D. Pedro, Aveiro (HIP), na Unidade de Hipertensão e Risco CV do Hospital Pedro Hispano (HPH), Matosinhos e na Clínica Cross/Moss do Porto. O objectivo principal deste estudo foi avaliar, nesta população, seguida durante 8- 12 anos, o valor preditivo de morbi-mortalidade CV da pressurometria ambulatória de 24 horas (MAPA), nomeadamente de diversos índices e valores dela extraída, tais como: (i) valores médios da pressão arterial (PA) de 24-h, diurna e nocturna; (ii) queda tensional noctuma, (iii) diferentes padrões de queda tensional nocturna em particular do padrão Non Dipper; (iv) PA diferencial de 24h, diurna e nodurna; (v) frequência cardíaca de 24 horas (vi) Ambulatory Arterial Stifness. Foram incluídos registos de MAPA de 1200 doentes, de um total de 2644, dos quais 53,8% eram mulheres e 10,2% eram diabéticos. Ao longo de um follow up médio de 8,2+3,0 anos, verificaram-se 62 óbitos e 152 eventos CV fatais e não fatais compreendendo 79 AVC, 51 eventos coronários e 22 classificados de outros eventos cardiovasculares. O estudo permitiu concluir que: 1- A MAPA foi superior a PA casual como preditor de eventos CV globais e de acidentes cerebrovasculares (AVC). 2 - De entre os valores da MAPA, o valor preditivo dos valores sistólicos (de 24 h, diurnos e nocturnos) foi superior ao dos respectivos valores diastólicos e o dos valores nocturnos foi superior ao dos valores diurnos. 3 - 0s eventos CV totais e os eventos coronários foram mais frequentes nos homens do que nas mulheres, sem diferença relativamente ao AVC. O valor preditivo independente da MAPA (sobretudo da PAS e da PP24h) foi superior nas mulheres vs homens relativamente aos eventos globais e AVC. 4- 0s padrões non-dipper e reverted-dipper de queda tensional nocturna associaram-se a pior prognóstico cardiovascular, relativamente ao padrão dipper. Contudo, dentro do padrão non-dipper, somente os doentes com queda tensional nocturna entre 0-4,9% -non-dippers 1 (mas não os doentes com queda tensional nocturna entre 5,O-9,9% -non-dippers 2) apresentaram risco CV superior ao do padrão dipper e semelhante ao do padrão reverted-dipper. Este achado poderá implicar a reclassificação do padrão non-dipper e do risco CV a ele associado. 5- O índice de rigidez arterial derivado da MAPA (AASI) correlaciona-se com outros índices (ex. a velocidade da onda de pulso) e contribui para estratificar o risco CV (eventos CV e AVC). O valor preditivo CV do AASI não é globalmente superior ao da PP 24h, embora em alguns casos o AASI possa acrescentar informação prognostica adicional a PP.

Determinants of left ventricular mass as measured by Doppler echocardiography in pre-adolescents

This study examined factors contributing to the differences in left ventricular mass as measured by Doppler echocardiography in children. Fourteen boys (10.3 ± 0.3 years of age) and 1 1 girls (10.5 ± 0.4 years of age) participated in the study. Height and weight were measured, and relative body fat was determined from the measurement of skinfold thickness according to Slaughter et al. (1988). Lean Body Mass was then calculated by subtracting the fat mass from the total body mass. Sexual maturation was self-assessed using the stages of sexual maturation by Tanner (1962). Both pubic hair development and genital (penis or breast for boys and girls respectively) development were used to determine sexual maturation. Carotid Pulse pressure was assessed by applanation tomometry in the left carotid artery. Cardiac mass was measured by Doppler Echocardiography. Images of cardiac structures were taken using B-Mode and were then translated to M- Mode. The dimensions at the end diastole were obtained at the onset of the QRS complex of the electrocardiogram in a plane through a standard position. Measurements included: (a) the diameter of the left ventricle at the end diastole was measured from the septum edge to the endocardium mean border, (b) the posterior wall was measured as the distance from to anterior wall to the epicardium surface, and (c) the interventricular septum was quantified as the distance from the surface of the left ventricle border to the right ventricle septum surface. Systolic time measurements were taken at the peak of the T-wave of the electrocardiogram. Each measurement was taken three to five times before averaging. Average values were used to calculate cardiac mass using the following equation (Deveraux et al. 1986). Weekly physical activity metabolic equivalent was calculated using a standardize activity questionnaire (Godin and Shepard, 1985) and peakV02 was measured on a cycloergometer. There were no significant differences in cardiovascular mesurements between boys and girls. Left ventricular mass was correlated (p<0.05) with size, maturation, peakV02 and physical activity metabolic equivalent. In boys, lean body mass alone explained 36% of the variance in left ventricular mass while weight was the single strongest predictor of left ventricular mass (R =0.80) in girls. Lean body mass, genital developemnt and physical activity metabolic equivalent together explained 46% and 81% in boys and girls, respectively. However, the combination of lean body mass, genital development and peakV02 (ml kgLBM^ min"') explained up to 84% of the variance in left ventricular mass in girls, but added nothing in boys. It is concluded that left ventricular mass was not statistically different between pre-adolescent boys and girls suggesting that hormonal, and therefore, body size changes in adolescence have a main effect on cardiac development and its final outcome. Although body size parameters were the strongest correlates of left ventricular mass in this pre-adolescent group of children, to our knowledge, this is the first study to report that sexual maturation, as well as physical activity and fitness, are also strong associated with left ventricular mass in pre-adolescents, especially young females. Arterial variables, such as systolic blood pressure and carotid pulse pressure, are not strong determinants of left ventricular mass in this pre-adolescent group. In general, these data suggest that although there is no gender differences in the absolute values of left ventricular mass, as children grow, the factors that determine cardiac mass differ between the genders, even in the same pre-adolescent age.