Log-ratio transformations for dietary compositions: numerical and conceptual questions.

When evaluating the impact of macronutrient intakes on health outcomes, researchers in nutritional epidemiology are mostly interested in two types of information: the relative importance of the individual macronutrients and the absolute effect of total energy intake. However, the usual substitution models do not allow these separate effects to be disentangled. Dietary data are typical examples of compositional data, which convey relative information and are, therefore, meaningfully expressed in the form of ratios. Various formulations of log-ratios have been proposed as a means of analysing compositional data, and their interrelationships when they are used as predictors in regression models have been previously reported. This note describes the application of distinct log-ratio transformations to the composition of dietary macronutrients and discusses the interpretative implications of using them as explanatory variables in regression models together with a term for the total composition (total energy intake). It also provides examples that consider serum glucose levels as the health outcome and are based on data coming from an Italian population-based study. The log-ratio transformation of dietary data has both numerical and conceptual advantages, and overcomes the drawbacks of traditional substitution models.

Using inferences concerning the effects of nutrient balances to define outcome-related food scores.

AIM: To describe food scores that can be interpreted as indicators of the potential effects of a food on health outcomes. METHODS: The scores consist of weighted averages of the estimates of the association between a health outcome and nutrient balances. Each food contributes a set of weights depending on its nutrient composition. The nutrient balances of a food's constituents are defined in a manner that is similar to those included in the model from which the estimated associations are obtained. As the balances are based on log-ratios, the presence of zero observations is problematic, but observations recorded as trace (rounded zeros) can be suitably replaced by a small value. In order to overcome the essential zero problem, we propose a strategy that exploits the flexibility of sequential binary partitioning, a procedure used to define orthogonal balances, and also describe the estimates of the variance and confidence limits of food scores. RESULTS: Data from an Italian population-based study were used to provide examples regarding serum high-density lipoprotein and triglyceride levels and waist circumference values, and the scores calculated for some foods or groups of foods are shown. CONCLUSIONS: Food scores allow foods to be ranked on the basis of their potential effects on health outcomes and, as they are not directly related to the amount of the food consumed, may be less subject to confounding. The accuracy of the estimates depends on the completeness of the food's nutrient composition: that is, the more complete the nutrient composition, the more accurate the estimate.

Exploring the relationship between Nutrition, gUT microbiota, and BRain AgINg in community-dwelling seniors: the Italian NutBrain population-based cohort study protocol.

BACKGROUND: Epidemiological evidence suggests that healthy diet is associated with a slowdown of cognitive decline leading to dementia, but the underlying mechanisms are still partially unexplored. Diet is the main determinant of gut microbiota composition, which in turn impacts on brain structures and functions, however to date no studies on this topic are available. The goal of the present paper is to describe the design and methodology of the NutBrain Study aimed at investigating the association of dietary habits with cognitive function and their role in modulating the gut microbiota composition, and brain measures as well. METHODS/DESIGN: This is a population-based cohort study of community-dwelling adults aged 65 years or more living in Northern Milan, Italy. At the point of presentation people are screened for cognitive functions. Socio-demographic characteristics along with lifestyles and dietary habits, medical history, drugs, functional status, and anthropometric measurements are also recorded. Individuals suspected to have cognitive impairment at the screening phase undergo a clinical evaluation including a neurological examination and a Magnetic Resonance Imaging (MRI) scanning (both structural and functional). Stool and blood samples for the gut microbiota analysis and for the evaluation of putative biological markers are also collected. For each subject with a confirmed diagnosis of Mild Cognitive Impairment (MCI), two cognitively intact controls of the same sex and age are visited. We intend to enrol at least 683 individuals for the screening phase and 240 persons for the clinical assessment. DISCUSSION: The NutBrain is an innovative study that incorporates modern and advanced technologies (i.e. microbiome and neuroimaging) into traditional epidemiologic design. The study represents a unique opportunity to address key questions about the role of modifiable risk factors on cognitive impairment, with a particular focus on dietary habits and their association with gut microbiota and markers of the brain-aging process. These findings will help to encourage and plan lifestyle interventions, for both prevention and treatment, aiming at promoting healthy cognitive ageing. TRIAL REGISTRATION: Trial registration number NCT04461951 , date of registration July 7, 2020 (retrospectively registered, ClinicalTrials.gov ).

Serum cholesterol elasticities in relation to macro- and micronutrient balances.

The application of the isometric log-ratio (ilr) transformation to dietary data leads to the definition of nutrient balances that represent new variables which can be included in regression models as covariates. However, their effects on the response variable are not easy to quantify. We then propose borrowing the concept of elasticity from econometrics as an appealing means of improving the interpretability of the ilr-related coefficients. Using data from an Italian population-based study, a multiple linear regression model of the serum total-/HDL-cholesterol ratio on nutrient balances was fitted and the estimated coefficients were used to derive elasticities. The elasticities measure the relative changes in the cholesterol ratio in response to the relative changes in specific nutrient ratios, while keeping unchanged the proportional relationships between the other dietary elements. In a comprehensive overview of the diet, this alternative approach to dietary data analysis allows isocaloric analysis and may provide interesting new insights.

Compositional data analysis as an alternative paradigm for nutritional studies.

BACKGROUND & AIM: Although the compositional nature of dietary data is well recognized, little attention has been given to the methods specifically developed for the statistical analysis of compositional data. The use of standard statistical procedures that ignore the relative nature of compositional elements can lead to spurious results when applied to crude data. This note proposes using a compositional data approach for the statistical analysis of nutritional data. METHODS: The analyses of data from an Italian population study of 673 non-diabetic women aged 40-74 years were based on isometric log-ratio (ilr) transformation applied to three dietary compositions: seven-part macronutrients, nine-part vitamins and six-part minerals. The ilr transformation produces new variables that represent specific contrasts (balances) between the compositional parts. Different sequential binary partitions have been described and used as a means of flexibly defining balances on the basis of a researcher's interest, and the new variables (that are suitable for undergoing standard statistical procedures) have been included as covariates in linear regression models in order to examine the isocaloric associations between specific dietary balances and waist circumference (WC). RESULTS: Regardless of the dietary compositions, total energy was positively and fibre intake was negatively associated with WC. Net of these effects and keeping constant the proportional relationships between the other dietary components, WC was negatively associated with the relative increase in starches, and positively associated with the relative niacin content. Vitamin C was negatively associated with WC, whereas folate content was positively related. DISCUSSION: The proposed approach allows a clear interpretation of the relative roles of different dietary components within a holistic overview of a diet. The analyses involving WC provide some useful insights.

Discontinuation of anti-hypertensive drugs increases 11-year cardiovascular mortality risk in community-dwelling elderly (the Bambuí Cohort Study of Ageing).

BACKGROUND: Hypertension remains a major public health problem whose management is hampered by poor persistence with pharmacological therapy. The aim of this study was to evaluate the association between discontinuing antihypertensive drugs (AHDs) and the risk of cardiovascular mortality in the elderly. METHODS: A population-based prospective cohort study of all of the ≥ 60-year-old residents in Bambuí city (Brazil) enrolled 1606 subjects (92.2%), of whom 1494 (93.0%) were included in this study. The use of AHDs was ascertained annually in a real-clinical context, and time-varying AHD exposure was categorised as non-use, current use or stopped. The predicted cardiovascular mortality rates were estimated using interval Poisson models for ungrouped person-time data, taking into account current levels of systolic blood pressure (BP). RESULTS: The overall adjusted cardiovascular mortality risk ratio of AHD stoppers vs current users was 3.12 (95% CI: 2.35-4.15). There was a significant interaction with BP levels: the association between discontinuing AHDs and the risk of cardiovascular mortality was stronger at higher systolic BP levels. The estimates of the risk of cardiovascular mortality over the follow-up period were similar in AHD users and non-users, for whom AHDs were never prescribed. CONCLUSION: Discontinuing AHDs increases the risk of cardiovascular mortality in the elderly. Misconceptions about symptoms or drug-related adverse effects could underlie a subject's decision to discontinue AHDs. Greater attention should be paid to the choice of AHDs and informative action.

Effects of interactions between ApoE polymorphisms, alcohol consumption and obesity on age-related trends of blood pressure levels in postmenopausal women: the Bambuì cohort study of aging (1997-2008).

OBJECTIVES: To evaluate the effects of interactions between ApoE genotypes, alcohol consumption and obesity on the age-related trends of blood pressure (BP) levels in postmenopausal women. STUDY DESIGN: A population-based prospective cohort study of all residents in Bambuì, south-eastern Brazil, aged 60 years or older. Repeated BP measurements were obtained in four waves from 851 women who underwent ApoE genotyping at baseline (88.3% of those enrolled), and multi-level random-effects pattern-mixture models were used to evaluate the age-related BP trajectories, while accounting for non-ignorable dropouts/deaths and handling heterogeneities as random parameter variations. The few measurements (2.1%) made during hormone replacement therapy were excluded from the analysis. RESULTS: Alcohol consumption was associated with high levels of systolic and diastolic BP in an age×genotype-dependent manner only in the non-obese women (BMI<27 kg/m(2)). Among those with the ɛ3/3 genotype, the differences in systolic and diastolic levels between drinkers and non-drinkers estimated at the age of 60 years were respectively 13.7 mmHg (p=0.022) and 10.7 mmHg (p=0.002), and disappeared in the older age groups, in which drinking was associated with systolic/diastolic hypertension if the non-obese women were ɛ4 carriers. CONCLUSION: In non-obese postmenopausal women, alcohol consumption is associated with systolic and diastolic hypertension early in those with the ɛ3/3 ApoE genotype, and late in ɛ4 carriers. We hypothesize the mediation of androgen hormones and the influence of ApoE genotypes on age at natural menopause. A better understanding of these mechanisms may guide better preventive choices.

Fibrinogen, hematocrit, platelets in mild kidney dysfunction and the role of uric acid: an Italian male population study.

AIM: To examine the relationship between some blood parameters and mild kidney dysfunction. PARTICIPANTS AND METHODS: A total of 719 Italian men aged 42 to 74 years from a population-based survey carried out in the town of Bollate (Milan). General linear models were used to examine the variations in plasma fibrinogen, hematocrit, platelet counts, mean platelet volume, and uric acid across levels of kidney function (estimated on the basis of glomerular filtration rate [GFR]), adjusting for age, education, smoking, alcohol consumption, physical activity (evaluated as TV watching, engaging in sport practice, and walking/cycling), waist circumference, arm muscle area, high-density lipoprotein (HDL)-cholesterol, triglycerides, hypertension, diabetes, cardiovascular disease history, and nonsteroid anti-inflammatory, diuretic, and antihypertensive drug use. RESULTS: Plasma fibrinogen and hematocrit levels increased, and platelet counts and mean platelet volume significantly decreased as GFR fell to <80 or <70 mL/min per 1.73 m(2); stratified analysis revealed an association with serum uric acid levels. Alterations compatible with an increased cardiovascular risk were particularly evident among the participants with higher uric acid levels, whereas those indicative of platelet dysfunction were found among participants with lower levels. CONCLUSIONS: Parameters affecting hemostasis and blood viscosity are altered when kidney function is only slightly reduced, and the patterns of these relationships seem to be influenced by the levels of serum uric acid, whose easy and inexpensive measurement could have prognostic value.