Anthony P. Fitzgerald

Gut microbiota composition correlates with diet and health in the elderly

Alterations in intestinal microbiota composition are associated with several chronic conditions, including obesity and inflammatory diseases. The microbiota of older people displays greater inter-individual variation than that of younger adults. Here we show that the faecal microbiota composition from 178 elderly subjects formed groups, correlating with residence location in the community, day-hospital, rehabilitation or in long-term residential care. However, clustering of subjects by diet separated them by the same residence location and microbiota groupings. The separation of microbiota composition significantly correlated with measures of frailty, co-morbidity, nutritional status, markers of inflammation and with metabolites in faecal water. The individual microbiota of people in long-stay care was significantly less diverse than that of community dwellers. Loss of community-associated microbiota correlated with increased frailty. Collectively, the data support a relationship between diet, microbiota and health status, and indicate a role for diet-driven microbiota alterations in varying rates of health decline upon ageing.

European guidelines on cardiovascular disease prevention in clinical practice

Guidelines aim to present all the relevant evidence on a particular issue in order to help physicians to weigh the benefits and risks of a particular diagnostic or therapeutic procedure. They should be helpful in everyday clinical decision-making. A great number of guidelines have been issued in recent years by different organisations--European Society of Cardiology (ESC), American Heart Association (AHA), American College of Cardiology (ACC), and other related societies. By means of links to web sites of National Societies several hundred guidelines are available. This profusion can put at stake the authority and validity of guidelines, which can only be guaranteed if they have been developed by an unquestionable decision-making process. This is one of the reasons why the ESC and others have issued recommendations for formulating and issuing guidelines. In spite of the fact that standards for issuing good quality guidelines are well defined, recent surveys of guidelines published in peer-reviewed journals between 1985 and 1998 have shown that methodological standards were not complied with in the vast majority of cases. It is therefore of great importance that guidelines and recommendations are presented in formats that are easily interpreted. Subsequently, their implementation programmes must also be well conducted. Attempts have been made to determine whether guidelines improve the quality of clinical practice and the utilisation of health resources. In addition, the legal implications of medical guidelines have been discussed and examined, resulting in position documents, which have been published by a specific task force. The ESC Committee for practice guidelines (CPG) supervises and coordinates the preparation of new guidelines and expert consensus documents produced by task forces, expert groups or consensus panels. The Committee is also responsible for the endorsement of these guidelines or statements.

Composition, variability, and temporal stability of the intestinal microbiota of the elderly

Alterations in the human intestinal microbiota are linked to conditions including inflammatory bowel disease, irritable bowel syndrome, and obesity. The microbiota also undergoes substantial changes at the extremes of life, in infants and older people, the ramifications of which are still being explored. We applied pyrosequencing of over 40,000 16S rRNA gene V4 region amplicons per subject to characterize the fecal microbiota in 161 subjects aged 65 y and older and 9 younger control subjects. The microbiota of each individual subject constituted a unique profile that was separable from all others. In 68% of the individuals, the microbiota was dominated by phylum Bacteroides, with an average proportion of 57% across all 161 baseline samples. Phylum Firmicutes had an average proportion of 40%. The proportions of some phyla and genera associated with disease or health also varied dramatically, including Proteobacteria, Actinobacteria, and Faecalibacteria. The core microbiota of elderly subjects was distinct from that previously established for younger adults, with a greater proportion of Bacteroides spp. and distinct abundance patterns of Clostridium groups. Analyses of 26 fecal microbiota datasets from 3-month follow-up samples indicated that in 85% of the subjects, the microbiota composition was more like the corresponding time-0 sample than any other dataset. We conclude that the fecal microbiota of the elderly shows temporal stability over limited time in the majority of subjects but is characterized by unusual phylum proportions and extreme variability.

Prospective Study of Microalbuminuria as Predictor of Mortality in NIDDM

Retrospective studies of patients with non-insulin-dependent diabetes mellitus (NIDDM) have suggested that microalbuminuria predicts early all-cause (mainly cardiovascular) mortality independently of arterial blood pressure. These findings have not been confirmed in prospective studies, and it is not known whether the predictive power of microalbuminuria is independent of other major cardiovascular risk factors. During 1985–1987, we examined a representative group of 141 nonproteinuric patients with NIDDM for the prevalence of coronary heart disease and several of its established and putative risk factors, including raised urinary albumin excretion (UAE) rate. Thirty-six patients had microalbuminuria (UAE 20–200 μg/min), and 105 had normal UAE (< 20 μg/min). At follow-up, an average of 3.4 yr later, 14 patients had died. There was a highly significant excess mortality (chiefly from cardiovascular disease) among those with microalbuminuria (28%) compared to those without microalbuminuria (4%, P < 0.001). In univariate survival analysis, significant predictors of all-cause mortality included microalbuminuria (P < 0.001), hypercholesterolemia (P < 0.01), hypertriglyceridemia (P < 0.05), and preexisting coronary heart disease (P < 0.05). The predictive power of microalbuminuria persisted after adjustment for the effects of other major risk factors (P < 0.05). We conclude that microalbuminuria is a significant risk marker for mortality in NIDDM, independent of the other risk factors examined. Its presence can be regarded as an index of increased cardiovascular vulnerability and a signal for vigorous efforts at correction of known risk factors.

Estimation of the dietary requirement for vitamin D in healthy adults

BACKGROUND Knowledge gaps have contributed to considerable variation among international dietary recommendations for vitamin D. OBJECTIVE We aimed to establish the distribution of dietary vitamin D required to maintain serum 25-hydroxyvitamin D [25(OH)D] concentrations above several proposed cutoffs (ie, 25, 37.5, 50, and 80 nmol/L) during wintertime after adjustment for the effect of summer sunshine exposure and diet. DESIGN A randomized, placebo-controlled, double-blind 22-wk intervention study was conducted in men and women aged 20-40 y (n = 238) by using different supplemental doses (0, 5, 10, and 15 microg/d) of vitamin D(3) throughout the winter. Serum 25(OH)D concentrations were measured by using enzyme-linked immunoassay at baseline (October 2006) and endpoint (March 2007). RESULTS There were clear dose-related increments (P < 0.0001) in serum 25(OH)D with increasing supplemental vitamin D(3). The slope of the relation between vitamin D intake and serum 25(OH)D was 1.96 nmol x L(-1) x microg(-1) intake. The vitamin D intake that maintained serum 25(OH)D concentrations of >25 nmol/L in 97.5% of the sample was 8.7 microg/d. This intake ranged from 7.2 microg/d in those who enjoyed sunshine exposure, 8.8 microg/d in those who sometimes had sun exposure, and 12.3 microg/d in those who avoided sunshine. Vitamin D intakes required to maintain serum 25(OH)D concentrations of >37.5, >50, and >80 nmol/L in 97.5% of the sample were 19.9, 28.0, and 41.1 microg/d, respectively. CONCLUSION The range of vitamin D intakes required to ensure maintenance of wintertime vitamin D status [as defined by incremental cutoffs of serum 25(OH)D] in the vast majority (>97.5%) of 20-40-y-old adults, considering a variety of sun exposure preferences, is between 7.2 and 41.1 microg/d.

Calibración de la tabla SCORE de riesgo cardiovascular para España

Introduccion y objetivos La tercera Task Force Conjunta Europea de prevencion cardiovascular recomendo el uso de la funcion de riesgo SCORE de prediccion del riesgo de muerte cardiovascular en 10 anos para la toma de decisiones en las intervenciones clinicas. El objetivo de este estudio es calibrar dicha funcion para Espana. Metodos Se desarrollo un modelo aplicando las hazard ratio de muerte cardiovascular en 10 anos de las cohortes del estudio SCORE a los valores medios especificos por la edad y el sexo de los factores de riesgo del tercer examen del estudio MONICA-Cataluna (1994- 1996) y a las funciones de supervivencia cardiovascular en 10 anos de la poblacion espanola basadas en la mortalidad del ano 2002. Resultados El riesgo estimado mediante la funcion calibrada SCORE fue un 13% mas alto que el estimado con la funcion de bajo riesgo, aunque las diferencias entre ambas oscilaron segun la edad, el sexo y especialmente el tabaco. La tabla SCORE calibrada identifico 32 situaciones de alto riesgo no reconocidas en la tabla original SCORE de bajo riesgo, aunque el 50% tenia una prevalencia baja o nula. El porcentaje maximo de sujetos nuevamente identificados de alto riesgo con la tabla calibrada fue del 22%, observandose mas diferencias en los varones mayores de 55 anos. Conclusiones Mientras no se disponga de estimaciones del riesgo basadas en cohortes poblacionales espanolas suficientemente grandes, la utilizacion de las funciones originales de riesgo cardiovascular calibradas para el pais permitiria adoptar decisiones clinicas y de salud publica adecuadas.

Estimation of the dietary requirement for vitamin D in free-living adults ≥64 y of age

BACKGROUND Older adults may be more prone to developing vitamin D deficiency than younger adults. Dietary requirements for vitamin D in older adults are based on limited evidence. OBJECTIVE The objective was to establish the dietary intake of vitamin D required to maintain serum 25-hydroxyvitamin D [25(OH)D] concentrations above various cutoffs between 25 and 80 nmol/L during wintertime, which accounted for the effect of summer sunshine exposure and diet. DESIGN A randomized, placebo-controlled, double-blind, 22-wk intervention was conducted in men and women aged >/=64 y (n = 225) at supplemental levels of 0, 5, 10, and 15 microg vitamin D(3)/d from October 2007 to March 2008. RESULTS Clear dose-related increments (P < 0.0001) in serum 25(OH)D were observed with increasing supplemental vitamin D(3) intakes. The slope of the relation between total vitamin D intake and serum 25(OH)D was 1.97 nmol . L(-1) . microg intake(-1). The vitamin D intake that maintained serum 25(OH)D concentrations >25 nmol/L in 97.5% of the sample was 8.6 microg/d. Intakes were 7.9 and 11.4 microg/d in those who reported a minimum of 15 min daily summer sunshine exposure or less, respectively. The intakes required to maintain serum 25(OH)D concentrations of >37.5, >50, and >80 nmol/L in 97.5% of the sample were 17.2, 24.7, and 38.7 microg/d, respectively. CONCLUSION To ensure that the vitamin D requirement is met by the vast majority (>97.5%) of adults aged >/=64 y during winter, between 7.9 and 42.8 microg vitamin D/d is required, depending on summer sun exposure and the threshold of adequacy of 25(OH)D. This trial was registered at http://www.controlled-trials.com/ISRCTN20236112 as ISRCTN registration no. ISRCTN20236112.

Defining Metabolically Healthy Obesity: Role of Dietary and Lifestyle Factors

Background There is a current lack of consensus on defining metabolically healthy obesity (MHO). Limited data on dietary and lifestyle factors and MHO exist. The aim of this study is to compare the prevalence, dietary factors and lifestyle behaviours of metabolically healthy and unhealthy obese and non-obese subjects according to different metabolic health criteria. Method Cross-sectional sample of 1,008 men and 1,039 women aged 45-74 years participated in the study. Participants were classified as obese (BMI ≥30kg/m2) and non-obese (BMI <30kg/m2). Metabolic health status was defined using five existing MH definitions based on a range of cardiometabolic abnormalities. Dietary composition and quality, food pyramid servings, physical activity, alcohol and smoking behaviours were examined. Results The prevalence of MHO varied considerably between definitions (2.2% to 11.9%), was higher among females and generally increased with age. Agreement between MHO classifications was poor. Among the obese, prevalence of MH was 6.8% to 36.6%. Among the non-obese, prevalence of metabolically unhealthy subjects was 21.8% to 87%. Calorie intake, dietary macronutrient composition, physical activity, alcohol and smoking behaviours were similar between the metabolically healthy and unhealthy regardless of BMI. Greater compliance with food pyramid recommendations and higher dietary quality were positively associated with metabolic health in obese (OR 1.45-1.53 unadjusted model) and non-obese subjects (OR 1.37-1.39 unadjusted model), respectively. Physical activity was associated with MHO defined by insulin resistance (OR 1.87, 95% CI 1.19-2.92, p = 0.006). Conclusion A standard MHO definition is required. Moderate and high levels of physical activity and compliance with food pyramid recommendations increase the likelihood of MHO. Stratification of obese individuals based on their metabolic health phenotype may be important in ascertaining the appropriate therapeutic or intervention strategy.

How much does HDL cholesterol add to risk estimation? A report from the SCORE investigators

Background Systematic COronary Risk Evaluation (SCORE), the risk estimation system recommended by the European guidelines on cardiovascular disease prevention, estimates 10-year risk of cardiovascular disease mortality based on age, sex, country of origin, systolic blood pressure, smoking status and either total cholesterol (TC) or TC/high-density lipoprotein cholesterol (HDL-C) ratio. As, counterintuitively, these two systems perform very similarly, we have investigated whether incorporating HDL-C and TC as separate variables improves risk estimation. Methods The study consisted of 57 302 men and 47 659 women. Cox proportional hazards method was used to derive the function including HDL-C and an identical function without HDL-C for comparison. Risk charts were developed to illustrate the results. Results Inclusion of HDL-C resulted in a modest but statistically significant improvement in risk estimation, based on the area under receiver operating characteristic curve (AUROC); 0.814 versus 0.808, P value less than 0.0001, for the functions with and without HDL-C, respectively. Addition of HDL-C also resulted in a significant and important improvement in risk estimation as measured by net reclassification index, which is highly clinically relevant. Improvement in risk estimation was greatest in women from high-risk countries, in terms of both AUROC and net reclassification index. Conclusion For the general population, the inclusion of HDL-C in risk estimation results in only a modest improvement in overall risk estimation based on AUROC. However, when using the more clinically that examines reclassification of individuals, clinically useful improvements occur. Inclusion of HDL may be particularly useful in women from high-risk countries and individuals with unusually high or low HDL-C levels. Addition of HDL-C is particularly applicable to electronic, interactive risk estimation systems such as HeartScore.

The incidence and repetition of hospital-treated deliberate self harm: findings from the world's first national registry.

Background Suicide is a significant public health issue with almost one million people dying by suicide each year worldwide. Deliberate self harm (DSH) is the single most important risk factor for suicide yet few countries have reliable data on DSH. We developed a national DSH registry in the Republic of Ireland to establish the incidence of hospital-treated DSH at national level and the spectrum and pattern of presentations with DSH and repetition. Methods and Findings Between 2003 and 2009, the Irish National Registry of Deliberate Self Harm collected data on DSH presentations to all 40 hospital emergency departments in the country. Data were collected by trained data registration officers using standard methods of case ascertainment and definition. The Registry recorded 75,119 DSH presentations involving 48,206 individuals. The total incidence rate fell from 209 (95% CI: 205–213) per 100,000 in 2003 to 184 (95% CI: 180–189) per 100,000 in 2006 and increased again to 209 (95% CI: 204–213) per 100,000 in 2009. The most notable annual changes were successive 10% increases in the male rate in 2008 and 2009. There was significant variation by age with peak rates in women in the 15–19 year age group (620 (95% CI: 605–636) per 100,000), and in men in the 20–24 age group (427 (95% CI: 416–439) per 100,000). Repetition rates varied significantly by age, method of self harm and number of previous episodes. Conclusions Population-based data on hospital-treated DSH represent an important index of the burden of mental illness and suicide risk in the community. The increased DSH rate in Irish men in 2008 and 2009 coincided with the advent of the economic recession in Ireland. The findings underline the need for developing effective interventions to reduce DSH repetition rates as a key priority for health systems.