Allostatic load as a marker of cumulative biological risk: MacArthur studies of successful aging

Allostatic load (AL) has been proposed as a new conceptualization of cumulative biological burden exacted on the body through attempts to adapt to life's demands. Using a multisystem summary measure of AL, we evaluated its capacity to predict four categories of health outcomes, 7 years after a baseline survey of 1,189 men and women age 70–79. Higher baseline AL scores were associated with significantly increased risk for 7-year mortality as well as declines in cognitive and physical functioning and were marginally associated with incident cardiovascular disease events, independent of standard socio-demographic characteristics and baseline health status. The summary AL measure was based on 10 parameters of biological functioning, four of which are primary mediators in the cascade from perceived challenges to downstream health outcomes. Six of the components are secondary mediators reflecting primarily components of the metabolic syndrome (syndrome X). AL was a better predictor of mortality and decline in physical functioning than either the syndrome X or primary mediator components alone. The findings support the concept of AL as a measure of cumulative biological burden.

Bone-marrow derived progenitor cells are associated with psychosocial determinants of health after controlling for classical biological and behavioral cardiovascular risk factors

BACKGROUND: Circulating progenitor cells have been implicated with maintaining vascular integrity. Low counts are found in adults with high cardiovascular risk and are associated with impaired endothelial function. It remains unknown whether psychosocial risk factors are independently related to counts of circulating progenitor cells. METHODS: We investigated a random sample of 468 adult industrial employees (mean age 41.2 years, 89% men) of Caucasian origin. Cardiovascular risk factors (blood pressure, LDL, HDL and C-reactive protein), health behavior (smoking, alcohol and physical exercise), psychological variables (effort-reward imbalance social support, negative affectivity) and interaction terms served as predictors of circulating progenitor cells (CD34+ CD31dim) as enumerated by flow-cytometry. FINDINGS: Psychosocial variables were independently associated with progenitor cell counts. The association with risk factors increased with age (explained variance in 18-36 year olds R(2)=0.17, p=0.55; age 36.1-46 R(2)=0.32, p=0.001; age>46 R(2)=0.27, p<0.001). Data revealed a shift from a larger association between behavioral and psychosocial variables and cell counts to a stronger association between biological variables and cell counts in older individuals. A significant interaction was observed between smoking and effort-reward imbalance in middle-aged subjects, those with both risk factors present had lower cell counts. In older employees, the interaction between biological risk factors and smoking was related to lower cell counts. INTERPRETATION: In working middle-aged and older men, psychosocial risk factors were related to circulating counts of progenitor cells. Smoking interacted negatively with psychosocial risk factors (middle-aged men) or with biological risk factors (older employees).

Risk-factors for antepartum fetal deaths in the city of São Paulo, Brazil

OBJECTIVE: To assess risk factors for antepartum fetal deaths. METHODS: A population-based case-control study was carried out in the city of São Paulo from August 2000 to January 2001. Subjects were selected from a birth cohort from a linked birth and death certificate database. Cases were 164 antepartum fetal deaths and controls were drawn from a random sample of 313 births surviving at least 28 days. Information was collected from birth and death certificates, hospital records and home interviews. A hierarchical conceptual framework guided the logistic regression analysis. RESULTS: Statistically significant factors associated with antepartum fetal death were: mother without or recent marital union; mother's education under four years; mothers with previous low birth weight infant; mothers with hypertension, diabetes, bleeding during pregnancy; no or inadequate prenatal care; congenital malformation and intrauterine growth restriction. The highest population attributable fractions were for inadequacy of prenatal care (40%), hypertension (27%), intrauterine growth restriction (30%) and absence of a long-standing union (26%). CONCLUSIONS: Proximal biological risk factors are most important in antepartum fetal deaths. However, distal factors - mother's low education and marital status - are also significant. Improving access to and quality of prenatal care could have a large impact on fetal mortality.

The expression level of BAALC-associated microRNA miR-3151 is an independent prognostic factor in younger patients with cytogenetic intermediate-risk acute myeloid leukemia.

Acute myeloid leukemia (AML) is a heterogeneous disease whose prognosis is mainly related to the biological risk conferred by cytogenetics and molecular profiling. In elderly patients (60 years) with normal karyotype AML miR-3151 have been identified as a prognostic factor. However, miR-3151 prognostic value has not been examined in younger AML patients. In the present work, we have studied miR-3151 alone and in combination with BAALC, its host gene, in a cohort of 181 younger intermediate-risk AML (IR-AML) patients. Patients with higher expression of miR-3151 had shorter overall survival (P=0.0025), shorter leukemia-free survival (P=0.026) and higher cumulative incidence of relapse (P=0.082). Moreover, in the multivariate analysis miR-3151 emerged as independent prognostic marker in both the overall series and within the unfavorable molecular prognostic category. Interestingly, the combined determination of both miR-3151 and BAALC improved this prognostic stratification, with patients with low levels of both parameters showing a better outcome compared with those patients harboring increased levels of one or both markers (P=0.003). In addition, we studied the microRNA expression profile associated with miR-3151 identifying a six-microRNA signature. In conclusion, the analysis of miR-3151 and BAALC expression may well contribute to an improved prognostic stratification of younger patients with IR-AML.

Contribution of modifiable risk factors to social inequalities in type 2 diabetes: prospective Whitehall II cohort study.

OBJECTIVE: To assess the contribution of modifiable risk factors to social inequalities in the incidence of type 2 diabetes when these factors are measured at study baseline or repeatedly over follow-up and when long term exposure is accounted for. DESIGN: Prospective cohort study with risk factors (health behaviours (smoking, alcohol consumption, diet, and physical activity), body mass index, and biological risk markers (systolic blood pressure, triglycerides and high density lipoprotein cholesterol)) measured four times and diabetes status assessed seven times between 1991-93 and 2007-09. SETTING: Civil service departments in London (Whitehall II study). PARTICIPANTS: 7237 adults without diabetes (mean age 49.4 years; 2196 women). MAIN OUTCOME MEASURES: Incidence of type 2 diabetes and contribution of risk factors to its association with socioeconomic status. RESULTS: Over a mean follow-up of 14.2 years, 818 incident cases of diabetes were identified. Participants in the lowest occupational category had a 1.86-fold (hazard ratio 1.86, 95% confidence interval 1.48 to 2.32) greater risk of developing diabetes relative to those in the highest occupational category. Health behaviours and body mass index explained 33% (-1% to 78%) of this socioeconomic differential when risk factors were assessed at study baseline (attenuation of hazard ratio from 1.86 to 1.51), 36% (22% to 66%) when they were assessed repeatedly over the follow-up (attenuated hazard ratio 1.48), and 45% (28% to 75%) when long term exposure over the follow-up was accounted for (attenuated hazard ratio 1.41). With additional adjustment for biological risk markers, a total of 53% (29% to 88%) of the socioeconomic differential was explained (attenuated hazard ratio 1.35, 1.05 to 1.72). CONCLUSIONS: Modifiable risk factors such as health behaviours and obesity, when measured repeatedly over time, explain almost half of the social inequalities in incidence of type 2 diabetes. This is more than was seen in previous studies based on single measurement of risk factors.

Parent Prediction of Autism Spectrum Disorder in Infants At Risk: A Follow-up Study

Later-born siblings of children with autism spectrum disorder (ASD) are considered at biological risk for ASD and the broader autism phenotype. Early screening may detect early signs of ASD and facilitate intervention as soon as possible. This follow-up study revisits and re-examines a second-degree autism screener for children at biological risk of autism, the Parent Observation Early Markers Scale (POEMS, Feldman et al., 2012). Using available follow-up information, 110 children (the original 108 infants plus 2 infants recruited after the completion of the original study) were divided into three groups: diagnosed group (n = 13), lost diagnosis group (n = 5), and undiagnosed group (n = 92). The POEMS continued to show acceptable predictive validity. The POEMS total scores and mean number of elevated items were significantly higher in the diagnosed group than the undiagnosed group. The lost diagnosis group did not differ from the undiagnosed group on POEMS total scores and elevated items at any age, but the lost diagnosis group had significantly lower total scores and number of elevated items than the diagnosed group starting at 18 months. Both ASD core and subsidiary behaviours differentiated the diagnosed and undiagnosed groups from 9−36 months of age. Using 70 as a cut-off score, sensitivity, specificity, and positive predictive value (PPV) were .69, .84, and .38, respectively. The study provides further evidence that the POEMS may serve as a low-cost early screener for ASD in at risk children and pinpoint specific developmental and behavioural problems that may be amenable to very early intervention.

Metabolic syndrome determinants in an urban population from Brazil: Social class and gender-specific interaction

Introduction: The metabolic syndrome (MS) is characterized by multiple cardiovascular risk factors such as central obesity, arterial hypertension, dislipidemia and hyperinsulinemia and is associated with a higher incidence of cardiovascular events and mortality. The aim of the present work is to describe the prevalence of MS in an urban population from a highly admixed developing country and to characterize the different correlations between this diagnosis, cardiovascular risk factors and demographic variables distributed in this population. Materials and methods: A cross-sectional study of risk factors for cardiovascular diseases was performed in the urban population of Vitoria, Brazil (n= 1507). Major cardiovascular risk factors such as smoking habits, alcohol intake, amount of physical activity, diabetes and hypertension were inquired. Blood biochemical assays were performed by standard techniques in 12 h fasting blood sample and Metabolic Syndrome (MS) was characterizes following the ATP III criteria. Results: The analysis of 1507 individuals showed a 25.43% general prevalence of MS without any significant difference between sexes, but a clear relation of the prevalence with progressing age (p=<0.0001). Even though both sexes showed similar prevalence rates, distribution of risk factors that defined MS was different between men and women, with the prevalence of hypertension, fasting hyperglycemia and hypertriglyceridemia being higher in men. Race was not an important risk factor for MS in this population as opposed to social economic class that was highly associated with the risk of MS in women as their social class was lower, but not in men. Conclusion: This cross-sectional study from a large urban population in Brazil showed a high general prevalence of MS (25.4%), which is increased as the population becomes older (especially in women) and poorer. Although prevalence was very similar in both genders, the frequency of components defining the syndrome varied greatly amongst them. In particular, a significant interaction between gender and social class was observed and may shed light in our understanding of the complex interplay between demographic and biological risk factors for metabolic syndrome. (C) 2007 Elsevier Ireland Ltd. All rights reserved.

Vascular diseases and old age mental disorders: an update of neuroimaging findings

Purpose of review To review neuroimaging findings that have been reported in samples of patients with cardiovascular disorders and their association with the onset of Alzheimer`s disease, vascular dementia, depression and bipolar disorder in the elderly and to highlight the implications of these findings to the knowledge about the pathophysiology of psychiatric disorders in old age, as well as their potential clinical implications. Recent findings Vascular risk factors, such as hypertension, diabetes, dyslipidemia, smoking habits and heart failure, have all been associated with signs of cerebrovascular dysfunction, including structural MRI findings of signal hyperintensities, lacunes and stroke and functional imaging findings of brain regional hypoperfusion and hypometabolism. Such brain abnormalities have been found to increase the risk of onset of psychiatric disorder (depression, bipolar and dementia) in old age. Summary As vascular risk factors are potentially modifiable when detected in midlife, the early characterization of brain changes associated with the presence of cardiovascular diseases holds promise to afford clinical applications in psychiatry, providing new perspectives for the prevention of old age psychiatric disorders.

Opportunities for the control of coronary heart disease in Australia

Objective: To estimate the number of coronary events that could be prevented in Australia each year by the use of preventive and therapeutic strategies targeted to subgroups of the population based on their levels of risk and need. Methods: Estimates of risk reduction from the published literature, prevalence estimates of elevated risk factor levels from the 1995 National Health Survey and treatment levels from the Australian collaborating centres in the World Health Organization's MONICA Project were used to calculate numbers of coronary events preventable among men and women aged 35-79 years in Australia. Results: Approximately 14,000 coronary events could be avoided each year if the mean level of cholesterol in the population was reduced by 0.5 mmol/L, smoking prevalence was halved and prevalence of physical inactivity was reduced to 25%. This represents a reduction in coronary events of about 40%. Even with less optimistic targets, a reduction of 20% could be attained, while the achievement of some internationally recommended targets could lead to almost 50% reduction. In the short term, aggressive medical treatment of people with elevated levels of risk factors and established coronary disease offers the greatest opportunity for reducing coronary events. Conclusion: A comprehensive approach to reduce levels of behavioural and biological risk factors and improve the use of effective treatment could lead to a large reduction in coronary event rates. In the long term, primary prevention - especially to reduce smoking, lower cholesterol levels and increase exercise - has the potential to reduce the population levels of risk and hence contain the national cost of coronary disease.

Estudo do sobre o impacto do risco biológico e ambiental na qualidade da interacção mãe-filho(a)

O presente estudo exploratório tem como principais objectivos: averiguar o impacto do risco biológico e ambiental, ou ambos, na interacção mãe-filho(a), e contribuir para a adaptação de uma escala de observação da qualidade da interacção mãe-filho(a) em interacção livre. Para o efeito observámos 40 díades mãe-filho(a) em jogo livre distribuídas por 4 grupos de estudo: o primeiro grupo composto por 14 díades sem condições assinaláveis de risco, o segundo grupo composto por 8 díades assinaláveis de risco biológico, o terceiro grupo composto por 7 díades em risco ambiental e por fim, o quarto grupo por 10 díades em risco ambiental e biológico. A recolha de dados foi realizada nos concelhos do Porto e Viseu. A qualidade de interacção foi inicialmente observada em 50 casos com a Escala de Comportamentos Interactivos dos bebés e das mães em jogo livre (Fuertes, Faria, Oliveira-Costa & Soares, 2010), tendo sido posteriormente adaptada para condições de risco tomando a designação de escala Escala de Avaliação de Comportamentos Interactivos mãe-filho(a)-Adaptada para Condições de Risco (Fuertes & Canelhas, 2011). Os comportamentos maternos e infantis foram cotados, independentemente, relativamente à expressão facial, expressão vocal, expressão afectiva, posicionamento, directividade e jogo. Os resultados foram analisados com recurso a estatística descritiva e multinominal. Os resultados do nosso estudo sugerem que as díades sem condições de risco tinham interacções mais positivas, recíprocas e ajustadas à idade das crianças, do que as díades sujeitas, quer a situações de risco biológico, quer a condições de risco ambiental. Adicionalmente, verificámos que alguns factores demográficos (e.g., risco na gravidez, área de residência, estabilidade profissional das mães e a frequência de creche (em oposição a amas) afectam a qualidade da interacção mãe-filho(a). Por fim, encontramos uma forte concordância entre as duas escalas, sugerindo que a nossa escala (Escala de Avaliação de Comportamentos Interactivos mãe-filho(a)-Adaptada para Situações de Risco), tem indicadores capazes de captar a natureza interactiva do jogo mãe-filho(a) e deverá ser validada.

Estudo da sensibilidade materna em díades de risco biológico, ambiental e acumulado

Dissertação apresentada na Escola Superior de Educação de Lisboa para obtenção de grau de Mestre em Intervenção Precoce

Slaughterhouses fungal burden assessment: a contribution for the pursuit of a better assessment strategy

In slaughterhouses, the biological risk is present not only from the direct or indirect contact with animal matter, but also from the exposure to bioaerosols. Fungal contamination was already reported from the floors and walls of slaughterhouses. This study intends to assess fungal contamination by cultural and molecular methods in poultry, swine/bovine and large animal slaughterhouses. Air samples were collected through an impaction method, while surface samples were collected by the swabbing method and subjected to further macro- and micro-scopic observations. In addition, we collected air samples using the impinger method in order to perform real-time quantitative PCR (qPCR) amplification of genes from specific fungal species, namely A. flavus, A. fumigatus and A. ochraceus complexes. Poultry and swine/bovine slaughterhouses presented each two sampling sites that surpass the guideline of 150 CFU/m3. Scopulariopsis candida was the most frequently isolated (59.5%) in poultry slaughterhouse air; Cladosporium sp. (45.7%) in the swine/bovine slaughterhouse; and Penicillium sp. (80.8%) in the large animal slaughterhouse. Molecular tools successfully amplified DNA from the A. fumigatus complex in six sampling sites where the presence of this fungal species was not identified by conventional methods. This study besides suggesting the indicators that are representative of harmful fungal contamination, also indicates a strategy as a protocol to ensure a proper characterization of fungal occupational exposure.

Factores de Risco Social, Comportamental e Biológico de Gravidez na Adolescência: Estudo de Caso-Controlo

Introdução: O melhor conhecimento dos factores de risco da gravidez na adolescência, especialmente a não desejada, pode ser uma forma de contribuir para a sua prevenção. Objectivo: Determinar possíveis factores de risco sociais, comportamentais e biológicos de gravidez na adolescência. Métodos: Estudo de caso-controlo comparando adolescentes grávidas (casos) com adolescentes que nunca estiveram grávidas (controlos). Foram analisados factores de risco (a) social: índice de Graffar, tipo de família, rendimento escolar e abandono escolar; (b) comportamental: hábitos de dependência, coitarca, contracepção e número de parceiros sexuais; e (c) biológico: idade, menarca, regularidade dos ciclos menstruais, índice de massa corporal e perturbações da saúde mental. Resultados: Foram incluídas 50 jovens em cada grupo, emparelhadas por idade. Os factores de risco de gravidez encontrados com significado estatístico foram (a) sociais: índice de Graffar ≥4 (OR: 4,96; IC 95%: 1,96-12,74), família não nuclear (OR: 4,64; IC 95%: 1,83-11,98), reprovações prévias (OR: 8,84; IC 95%: 3,20-25,16) e abandono escolar (OR: 9,01; IC 95%: 3,34-24,96); (b) comportamentais: hábitos de dependência (OR: 8,43; IC 95%: 1,65-57,87) e não utilização de contracepção (OR: 44,33; IC 95%: 5,05-100,92); e (c) biológicos: idade de menarca <12 anos (OR: 5,25; IC 95%: 1,89-15,02), irregularidade dos ciclos menstruais (OR: 4,51; IC 95%: 1,74-11,91) e índice de massa corporal >percentil 85 (OR: 2,95; IC 95%: 1,04-8,55). Não se revelaram factores de risco de gravidez a existência de mais de um parceiro sexual (OR: 4,42; IC: 0,5-99,31), idade de coitarca <15 anos (OR: 5,11; IC 95%: 0,93-36,71) e as perturbações da saúde mental (OR=1; IC 95%=0,15-6,63). Conclusão: Na promoção da saúde sexual e reprodutiva sugere-se que se dê atenção privilegiada às jovens de meio desfavorecido, de famílias não nucleares, com insucesso escolar, hábitos de dependência, idade menor de menarca, ausência de contracepção, irregularidade menstrual e excesso de peso.

Current genetic data do not improve the prediction of type 2 diabetes mellitus: the CoLaus study.

CONTEXT: Several genetic risk scores to identify asymptomatic subjects at high risk of developing type 2 diabetes mellitus (T2DM) have been proposed, but it is unclear whether they add extra information to risk scores based on clinical and biological data. OBJECTIVE: The objective of the study was to assess the extra clinical value of genetic risk scores in predicting the occurrence of T2DM. DESIGN: This was a prospective study, with a mean follow-up time of 5 yr. SETTING AND SUBJECTS: The study included 2824 nondiabetic participants (1548 women, 52 ± 10 yr). MAIN OUTCOME MEASURE: Six genetic risk scores for T2DM were tested. Four were derived from the literature and two were created combining all (n = 24) or shared (n = 9) single-nucleotide polymorphisms of the previous scores. A previously validated clinic + biological risk score for T2DM was used as reference. RESULTS: Two hundred seven participants (7.3%) developed T2DM during follow-up. On bivariate analysis, no differences were found for all but one genetic score between nondiabetic and diabetic participants. After adjusting for the validated clinic + biological risk score, none of the genetic scores improved discrimination, as assessed by changes in the area under the receiver-operating characteristic curve (range -0.4 to -0.1%), sensitivity (-2.9 to -1.0%), specificity (0.0-0.1%), and positive (-6.6 to +0.7%) and negative (-0.2 to 0.0%) predictive values. Similarly, no improvement in T2DM risk prediction was found: net reclassification index ranging from -5.3 to -1.6% and nonsignificant (P ≥ 0.49) integrated discrimination improvement. CONCLUSIONS: In this study, adding genetic information to a previously validated clinic + biological score does not seem to improve the prediction of T2DM.