Isabel Ferreira

Determinants of pulse wave velocity in healthy people and in the presence of cardiovascular risk factors: 'Establishing normal and reference values'

Aims Carotid–femoral pulse wave velocity (PWV), a direct measure of aortic stiffness, has become increasingly important for total cardiovascular (CV) risk estimation. Its application as a routine tool for clinical patient evaluation has been hampered by the absence of reference values. The aim of the present study is to establish reference and normal values for PWV based on a large European population. Methods and results We gathered data from 16 867 subjects and patients from 13 different centres across eight European countries, in which PWV and basic clinical parameters were measured. Of these, 11 092 individuals were free from overt CV disease, non-diabetic and untreated by either anti-hypertensive or lipid-lowering drugs and constituted the reference value population, of which the subset with optimal/normal blood pressures (BPs) (n = 1455) is the normal value population. Prior to data pooling, PWV values were converted to a common standard using established conversion formulae. Subjects were categorized by age decade and further subdivided according to BP categories. Pulse wave velocity increased with age and BP category; the increase with age being more pronounced for higher BP categories and the increase with BP being more important for older subjects. The distribution of PWV with age and BP category is described and reference values for PWV are established. Normal values are proposed based on the PWV values observed in the non-hypertensive subpopulation who had no additional CV risk factors. Conclusion The present study is the first to establish reference and normal values for PWV, combining a sizeable European population after standardizing results for different methods of PWV measurement.

Environmental correlates of physical activity in youth – a review and update

Obesogenic environments are thought to underlie the increased obesity prevalence observed in youth during the past decades. Understanding the environmental factors that are associated with physical activity (PA) in youth is needed to better inform the development of effective intervention strategies attempting to halt the obesity epidemic. We conducted a systematic semi‐quantitative review of 150 studies on environmental correlates of youth PA published in the past 25 years. The ANalysis Grid for Environments Linked to Obesity (ANGELO) framework was used to classify the environmental correlates studied. Most studies retrieved used cross‐sectional designs and subjective measures of environmental factors and PA. Variables of the home and school environments were especially associated with children’s PA. Most consistent positive correlates of PA were father’s PA, time spent outdoors and school PA‐related policies (in children), and support from significant others, mother’s education level, family income, and non‐vocational school attendance (in adolescents). Low crime incidence (in adolescents) was characteristic of the neighbourhood environment associated with higher PA. Convincing evidence of an important role for many other environmental factors was, however, not found. Further research should aim at longitudinal and intervention studies, and use more objective measures of PA and its potential (environmental) determinants.

Management of high blood pressure in children and adolescents: recommendations of the European Society of Hypertension

Hypertension in children and adolescents has gained ground in cardiovascular medicine, thanks to the progress made in several areas of pathophysiological and clinical research. These guidelines represent a consensus among specialists involved in the detection and control of high blood pressure in children and adolescents. The guidelines synthesize a considerable amount of scientific data and clinical experience and represent best clinical wisdom upon which physicians, nurses and families should base their decisions. They call attention to the burden of hypertension in children and adolescents, and its contribution to the current epidemic of cardiovascular disease, these guidelines should encourage public policy makers, to develop a global effort to improve identification and treatment of high blood pressure among children and adolescents.

Arterial stiffness in diabetes and the metabolic syndrome: a pathway to cardiovascular disease

Increased arterial stiffness associated with diabetes and the metabolic syndrome may in part explain the increased cardiovascular disease risk observed in these conditions. Arterial stiffness can be estimated by quantifying pulse pressure but is better described by distensibility and compliance coefficients, pulse wave velocity and wave reflection. The most common non-invasive methodologies used to quantify these estimates of arterial stiffness (e.g. ultrasonography and applanation tonometry) are also described. We then review and summarise the current data on the associations between diabetes, the metabolic syndrome and insulin resistance on the one hand and greater arterial stiffness on the other, and identify and discuss some unresolved issues such as differential stiffening of central vs peripheral arterial segments, the impact of sex, and the pathobiology of increased arterial stiffness in diabetes and the metabolic syndrome. Finally, some considerations with regard to treatment options are presented. At present the most powerful therapy available for reducing arterial stiffness is to vigorously treat hypertension using pharmacological agents. New pharmacological strategies to reduce arterial stiffness are likely to be especially relevant to individuals with diabetes.

Theory, evidence and Intervention Mapping to improve behavior nutrition and physical activity interventions.

BackgroundThe present paper intends to contribute to the debate on the usefulness and barriers in applying theories in diet and physical activity behavior-change interventions.DiscussionSince behavior theory is a reflection of the compiled evidence of behavior research, theory is the only foothold we have for the development of behavioral nutrition and physical activity interventions. Application of theory should improve the effectiveness of interventions. However, some of the theories we use lack a strong empirical foundation, and the available theories are not always used in the most effective way. Furthermore, many of the commonly-used theories provide at best information on what needs to be changed to promote healthy behavior, but not on how changes can be induced. Finally, many theories explain behavioral intentions or motivation rather well, but are less well-suited to explaining or predicting actual behavior or behavior change.For more effective interventions, behavior change theory needs to be further developed in stronger research designs and such change-theory should especially focus on how to promote action rather than mere motivation. Since voluntary behavior change requires motivation, ability as well as the opportunity to change, further development of behavior change theory should incorporate environmental change strategies.ConclusionIntervention Mapping may help to further improve the application of theories in nutrition and physical activity behavior change.

Mode and place of delivery, gastrointestinal microbiota, and their influence on asthma and atopy.

BACKGROUND Both gastrointestinal microbiota composition and cesarean section have been linked to atopic manifestations. However, results are inconsistent, and the hypothesized intermediate role of the microbiota in the association between birth mode and atopic manifestations has not been studied yet. OBJECTIVES We sought to investigate the relationship between microbiota composition, mode and place of delivery, and atopic manifestations. METHODS The Child, Parent and Health: Lifestyle and Genetic Constitution Birth Cohort Study included data on birth characteristics, lifestyle factors, and atopic manifestations collected through repeated questionnaires from birth until age 7 years. Fecal samples were collected at age 1 month (n = 1176) to determine microbiota composition, and blood samples were collected at ages 1 (n = 921), 2 (n = 822), and 6 to 7 (n = 384) years to determine specific IgE levels. RESULTS Colonization by Clostridium difficile at age 1 month was associated with wheeze and eczema throughout the first 6 to 7 years of life and with asthma at age 6 to 7 years. Vaginal home delivery compared with vaginal hospital delivery was associated with a decreased risk of eczema, sensitization to food allergens, and asthma. After stratification for parental history of atopy, the decreased risk of sensitization to food allergens (adjusted odds ratio, 0.52; 95% CI, 0.35-0.77) and asthma (adjusted odds ratio, 0.47; 95% CI, 0.29-0.77) among vaginally home-born infants was only found for children with atopic parents. Mediation analysis showed that the effects of mode and place of delivery on atopic outcomes were mediated by C difficile colonization. CONCLUSION Mode and place of delivery affect the gastrointestinal microbiota composition, which subsequently influences the risk of atopic manifestations.

Real-time quantitative PCR with SYBR Green I detection for estimating copy numbers of nine drug resistance candidate genes in Plasmodium falciparum

BackgroundEvaluating copy numbers of given genes in Plasmodium falciparum parasites is of major importance for laboratory-based studies or epidemiological surveys. For instance, pfmdr1 gene amplification has been associated with resistance to quinine derivatives and several genes involved in anti-oxidant defence may play an important role in resistance to antimalarial drugs, although their potential involvement has been overlooked.MethodsThe ΔΔCt method of relative quantification using real-time quantitative PCR with SYBR Green I detection was adapted and optimized to estimate copy numbers of three genes previously indicated as putative candidates of resistance to quinolines and artemisinin derivatives: pfmdr1, pfatp6 (SERCA) and pftctp, and in six further genes involved in oxidative stress responses.ResultsUsing carefully designed specific RT-qPCR oligonucleotides, the methods were optimized for each gene and validated by the accurate measure of previously known number of copies of the pfmdr1 gene in the laboratory reference strains P. falciparum 3D7 and Dd2. Subsequently, Standard Operating Procedures (SOPs) were developed to the remaining genes under study and successfully applied to DNA obtained from dried filter blood spots of field isolates of P. falciparum collected in São Tomé & Principe, West Africa.ConclusionThe SOPs reported here may be used as a high throughput tool to investigate the role of these drug resistance gene candidates in laboratory studies or large scale epidemiological surveys.

Cardiorespiratory fitness, physical activity, and arterial stiffness: the Northern Ireland Young Hearts Project.

Poor cardiorespiratory fitness and low physical activity have been identified as determinants of greater arterial stiffness, a mechanism that can partially explain the association of both variables with increased cardiovascular disease. However, the nature of these associations are not clear because cardiorespiratory fitness and physical activity can both mediate and confound the associations of one another with arterial stiffness. This issue was therefore examined in a population-based cohort of young adults. Subjects included 405 young men and women participating in an ongoing longitudinal study, the Northern Ireland Young Hearts Project. Pulse wave velocity was used to determine arterial stiffness in 2 arterial segments (aortoiliac and aortodorsalis pedis) using a noninvasive optical method. Cardiovascular fitness was estimated with a submaximal cycle test of physical work capacity and physical activity was estimated using a modified Baecke questionnaire. Associations were investigated with the use of multiple linear regression models with adjustment for potential confounders and/or intermediate variables. Cardiorespiratory fitness and sports-related physical activity (but not leisure- and work-related physical activity) were inversely associated with arterial stiffness in young adults. The associations between sports-related physical activity and arterial stiffness were strongly mediated by cardiorespiratory fitness, whereas physical activity levels did not disturb the associations between cardiopulmonary fitness and arterial stiffness. These findings suggest that arterial stiffness-related benefits of exercise are most likely to accrue if exercise prescription in young adults targets improvements in cardiorespiratory fitness.

Higher Plasma Levels of Advanced Glycation End Products Are Associated With Incident Cardiovascular Disease and All-Cause Mortality in Type 1 Diabetes: A 12-year follow-up study

OBJECTIVE To investigate the associations of plasma levels of advanced glycation end products (AGEs) with incident cardiovascular disease (CVD) and all-cause mortality in type 1 diabetes and the extent to which any such associations could be explained by endothelial and renal dysfunction, low-grade inflammation, and arterial stiffness. RESEARCH DESIGN AND METHODS We prospectively followed 169 individuals with diabetic nephropathy and 170 individuals with persistent normoalbuminuria who were free of CVD at study entry and in whom levels of Nε-(carboxymethyl)lysine, Nε-(carboxyethyl)lysine, pentosidine and other biomarkers were measured at baseline. The median follow-up duration was 12.3 (interquartile range 7.6–12.5) years. RESULTS During the course of follow-up, 82 individuals (24.2%) died; 85 (25.1%) suffered a fatal (n = 48) and/or nonfatal (n = 53) CVD event. The incidence of fatal and nonfatal CVD and of all-cause mortality increased with higher baseline levels of AGEs independently of traditional CVD risk factors: hazard ratio (HR) = 1.30 (95% CI = 1.03–1.66) and HR = 1.27 (1.00–1.62), respectively. These associations were not attenuated after further adjustments for markers of renal or endothelial dysfunction, low-grade inflammation, or arterial stiffness. CONCLUSIONS Higher levels of AGEs are associated with incident fatal and nonfatal CVD as well as all-cause mortality in individuals with type 1 diabetes, independently of other risk factors and of several potential AGEs-related pathophysiological mechanisms. Thus, AGEs may explain, in part, the increased cardiovascular disease and mortality attributable to type 1 diabetes and constitute a specific target for treatment in these patients.

Overexpression of Glyoxalase-I Reduces Hyperglycemia-induced Levels of Advanced Glycation End Products and Oxidative Stress in Diabetic Rats

The reactive advanced glycation end product (AGE) precursor methylglyoxal (MGO) and MGO-derived AGEs are associated with diabetic vascular complications and also with an increase in oxidative stress. Glyoxalase-I (GLO-I) transgenic rats were used to explore whether overexpression of this MGO detoxifying enzyme reduces levels of AGEs and oxidative stress in a rat model of diabetes. Rats were made diabetic with streptozotocin, and after 12 weeks, plasma and multiple tissues were isolated for analysis of AGEs, carbonyl stress, and oxidative stress. GLO-I activity was significantly elevated in multiple tissues of all transgenic rats compared with wild-type (WT) littermates. Streptozotocin treatment resulted in a 5-fold increase in blood glucose concentrations irrespective of GLO-I overexpression. Levels of MGO, glyoxal, 3-deoxyglucosone, AGEs, and oxidative stress markers nitrotyrosine, malondialdehyde, and F2-isoprostane were elevated in the diabetic WT rats. In diabetic GLO-I rats, glyoxal and MGO composite scores were significantly decreased by 81%, and plasma AGEs and oxidative stress markers scores were significantly decreased by ∼50%. Hyperglycemia induced a decrease in protein levels of the mitochondrial oxidative phosphorylation complex in the gastrocnemius muscle, which was accompanied by an increase in the lipid peroxidation product 4-hydroxy-2-nonenal, and this was counteracted by GLO-I overexpression. This study shows for the first time in an in vivo model of diabetes that GLO-I overexpression reduces hyperglycemia-induced levels of carbonyl stress, AGEs, and oxidative stress. The reduction of oxidative stress by GLO-I overexpression directly demonstrates the link between glycation and oxidative stress.