Association of Carotenoid Intake with Pulmonary Function.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is an inflammatory disease causing more than three million deaths annually around the world. Previous studies have shown an increased incidence of COPD among smokers. Studies also have shown antioxidant nutrients such as carotenoids, have been associated with lower rates of COPD. OBJECTIVE: To investigate if the consumption of carotenoids and carotenoid-rich foods is associated with higher pulmonary function. METHODS: Data were taken from the Atherosclerosis Risk in Communities (ARIC) study, which included approximately 15,000 individuals aged 45-64 years at baseline. Dietary intake of carotenoids and carotenoid-rich foods were assessed by food frequency questionnaire. Total carotenoid intake was calculated by summing five specific carotenoids: α-carotene, ß-carotene, ß-cryptoxanthin, lycopene, and lutein/zeaxanthin. Pulmonary function was evaluated as the ratio of forced expiratory volume in one second [FEV1] and forced vital capacity [FVC]. Linear regression analysis was used to assess the association between the intakes of carotenoids and carotenoid-rich foods and pulmonary function. Significance level was p < 0.05. RESULTS: A positive association between the total carotenoid intake with pulmonary function was only marginally significant; however, α-carotene, ß-carotene, and ß-cryptoxanthin were each positively associated (p = 0.001, p = 0.003, p = 0.007, respectively) with FEV1/FVC ratio in study participants. Food sources of these pro-vitamin A carotenes were also positively associated (p = 0.008) with FEV1/FVC ratio. CONCLUSIONS: This study suggests a possible role for the provitamin A carotenes, and their associated foods in improved pulmonary health.

Macronutrients Association with Change in Waist and Hip Circumference Over 9 Years.

OBJECTIVE: The calorie distribution of macronutrients affects individuals' health. Quantity and source of macronutrients may play major roles in waist circumference (WC) and hip circumference (HC). This study's purpose is to investigate the association between the quantity and source of macronutrients and the change in WC and HC over 9 years. METHODS: Participants (N = 11,343) were from the Atherosclerosis Risk in Community Study. Those diagnosed with cancer or a decrease in WC or HC of 15 cm or more over 9 years were excluded. Change scores were created for anthropometrics between clinic visits over 9 years. Macronutrient intakes were assessed by a food frequency questionnaire at visit 1 and presented as a percentage of energy intake. Linear regressions were performed with quartiles of dietary components on change scores for WC and HC with controlling cofactors. Gender subgroup analysis was performed. RESULTS: A larger increase in WC was associated with higher intakes of total carbohydrates, dietary fiber, and fructose (p for trend < 0.005). A smaller increase in WC was associated with higher intakes of sucrose, total protein, animal protein, and alcohol (p for trend < 0.02). A larger increase in HC was associated with higher intakes of total carbohydrate, sucrose, fructose, animal protein, and vegetable fat (p for trend < 0.05). A smaller increase in HC was associated with higher intakes of animal fat, total fat, and total protein (p for trend < 0.05). In males, changes in WC and HC were associated with fructose, sucrose, total fat, and total protein. In females, changes in WC and HC were associated with dietary fiber, fructose, alcohol, animal protein, total protein, animal fat, and vegetable fat. CONCLUSION: Macronutrient source and quantity play a significant role in individuals' adiposity and effects on WC and HC. Overall, an increase in WC and HC was seen over the 11 years. The source and quantity of the macronutrients play a significant role in WC and HC. Further research needs to be conducted to see the exact effect that macronutrients play on WC and HC.

A randomized trial of fish oil omega-3 fatty acids on arterial health, inflammation, and metabolic syndrome in a young healthy population.

BACKGROUND: Long chain omega-3 fatty acids from fish oils (O3) are known to have beneficial effects on a number of vascular risk factors in at-risk populations. The effects of a highly bioavailable emulsified preparation on an overweight young adult population are less well known. METHODS: Young adults, age 18-30, with body mass indices (BMIs) greater than 23 (average = 28.1) were administered 1.7 g of O3 per day (N = 30) or safflower oil placebo (N = 27) in an emulsified preparation (Coromega, Inc.) for 4 weeks in a double-blind randomized design. Blood was drawn and anthropometric measurements taken before and after dosing. Hemodynamic measures (central pulse wave velocity, augmentation index, and aortic systolic blood pressure), inflammatory cytokines (IL-6, IL-8, IL-10, and tumor necrosis factor-α), red blood cell and plasma phospholipid fatty acid profiles, fasting serum lipids, glucose, and C-reactive protein were measured. RESULTS: Red cell and plasma phospholipid eicosapentaenoic acid and docosahexaenoic acid concentrations increased over the four weeks of dosing in the O3 group. Dosing with O3 did not affect central pulse wave velocity, augmentation index, or aortic systolic blood pressure. None of the five American Heart Association metabolic syndrome components improved over the dosing period. None of the inflammatory cytokines, C-reactive protein, or lipids (total or LDL cholesterol) improved over the dosing period. CONCLUSIONS: No salutary effects of O3 were observed in hemodynamic, metabolic syndrome criteria or inflammatory markers as a result of this relatively short period of administration in this relatively overweight, but healthy young adult cohort.

DASH-like diets high in protein or monounsaturated fats improve metabolic syndrome and calculated vascular risk.

Weight-loss diets with varying proportions of macronutrients have had varying effects on weight loss, and components of metabolic syndrome and risk factors for vascular diseases. However, little work has examined the effect of weight-neutral dietary changes in macronutrients on these factors. This is an investigation using the OMNI Heart datasets available from the NHLBI BioLINCC program. This study compared a DASH-like diet high in carbohydrates with similar diets high in protein and high in unsaturated fats. Measures of metabolic syndrome, except waist, and measures of risk factors for vascular diseases were taken at the end of each dietary period. All 3 diets significantly lowered the number of metabolic syndrome components (p ≤ 0.002) with a standardized measure of changes in metabolic syndrome components, suggesting that the high-protein, high-fat diet was most efficacious overall (p = 0.035). All 3 diets lowered a calculated 10-year risk of cardiovascular disease, with the high-protein and unsaturated fat diet being the most efficacious (p < 0.001). Only the unsaturated fat diet showed a slightly decreased calculated 9-year risk of diabetes (p = 0.11). Of the 3 weight-neutral diets, those high in protein and unsaturated fats appeared partially or wholly most beneficial.

Body mass index mediates the association between meat intake and insulin sensitivity.

The purpose of this study was to examine the possible inverse relationship between total meat intake and processed meat intake and insulin sensitivity as mediated by body mass index (BMI). The Quantitative Insulin Sensitivity Check Index (QUICKI) was used to assess participants' insulin sensitivity: decreased insulin sensitivity indicated at a score of <0.36. Cross-sectional data were used from Visit 1 of the Atherosclerosis Risk in Communities (ARIC) cohort. Mediation analysis was conducted using the PROCESS macro for SPSS. The mean BMI was 27.3 ± 5.0 kg/m2, total meat intake was 1.76 ± 0.89 servings per day, processed meat intake was 0.44 ± 0.46 servings per day, and the mean QUICKI score was 0.34 ± 0.039. This suggested decreased insulin sensitivity was prevalent in this population. As hypothesized and previously shown, both total meat intake and processed meat were inversely and significantly associated with insulin sensitivity after adjusting for key covariates including BMI. In mediation analysis, the significant inverse direct association model between total meat and QUICKI was -0.0017 (95% CI: -0.0026, -0.0008). BMI had a significant indirect association with QUICKI of -0.0028 (95% CI: -0.0033, -0.0023) which accounted for 62% of the association between total meat intake and insulin sensitivity. In the processed meat intake and QUICKI mediation model, BMI accounted for a significant 43% of the relationship. Our results suggest that the association between total meat and processed meat intake and insulin sensitivity is mediated by BMI.

Prescribe by risk: the utility of a biomarker-based risk calculation in disease management to prevent heart disease.

Preventive treatment for those most at risk of heart disease rather than those with the highest blood pressure or cholesterol values may be a more efficacious strategy for disease management. This depends on accurate biomarker-based risk assessment tools. An evidence-based model of heart disease risk was developed using the Framingham model with an additional five risk factors, including three of the newer blood biomarkers. This was applied to the adult population of the 3rd National Health and Nutrition Examination Survey cohort. Additionally, the selection criteria for therapeutic intervention from the Adult Treatment Panel III guidelines (for hyperlipidemia) and the 7th Report of the Joint National Committee (for hypertension) were applied to the same subjects. Of this cohort 54% qualified for at least one of these medications while 18% qualified for both. Using this 18% cutoff, the 18% of the subjects with the highest calculated heart disease risk were also identified using the developed risk model. We applied established therapeutic reductions in heart disease probability to those identified by guidelines and to those identified by risk. Applying both drugs to the high-risk group (one third the size of the guidelines group) achieved the same reduction in population risk (about one fourth) as applying the drugs to the guideline groups and required only half as many prescriptions. Intermediate results were found when an intervention group was identified by a combination of both high risk and high levels of risk factors. In this simulation, identifying patients by heart disease risk level resulted in substantially fewer people being treated with fewer drugs and achieving a similar reduction in disease risk.

Accuracy of prediction models in the context of disease management.

There has been a significantly increased interest in the adoption of prediction modeling by many disease and case management programs to risk stratify members in order to optimize the utilization of available clinical resources. Before adopting any prediction model, it is critical to understand how to evaluate the model's accuracy. This paper explains the basic concepts of prediction accuracy, the relevant parameters, their drawbacks, and their interpretations. It also introduces a new accuracy parameter termed "cost concentration," which indicates the model accuracy more explicitly in the context of disease management.

Flavonol Intake and Cognitive Decline in Middle-Aged Adults.

Cognitive decline occurs with age and may be slowed by dietary measures, including increased intake of dietary phytochemicals. However, evidence from large and long-term studies of flavonol intake is limited. Dietary intakes of flavonols were assessed from a large biracial study of 10,041 subjects, aged 45-64, by analysis of a food frequency questionnaire administered at visit 1 of triennial visits. Cognitive function was assessed at visits 2 and 4 with the following three cognitive performance tests: the delayed word recall test, the revised Wechsler Adult Intelligence Scale digit symbol subtest, and the word fluency test of the Multilingual Aphasia Examination. The change in each score over 6 years was calculated, and a combined standardized change score was calculated. Generalized linear models controlled for age, ethnicity, gender, education level, energy intake, current smoking, physical activity, body mass index, diabetes, and vitamin C intake. Total flavonols across quintiles of intake were positively associated with preserved combined cognitive function (P<.001). This pattern with preserved combined cognitive function was consistent for the three major individual flavonols in the diet, myricetin, kaempferol, and quercetin (each P<.001). The positive association with total flavonols was strongest for the digit symbol subtest (P<.001). In this cohort, flavonol intake was correlated with protected cognitive function over time.

Adding multiple risk factors improves Framingham coronary heart disease risk scores.

PURPOSE: Since the introduction of the Framingham Risk Score (FRS), numerous versions of coronary heart disease (CHD) prediction models have claimed improvement over the FRS. Tzoulaki et al challenged the validity of these claims by illustrating methodology deficiencies among the studies. However, the question remains: Is it possible to create a new CHD model that is better than FRS while overcoming the noted deficiencies? To address this, a new CHD prediction model was developed by integrating additional risk factors, using a novel modeling process. METHODS: Using the National Health Nutritional Examination Survey III data set with CHD-specific mortality outcomes and the Atherosclerosis Risk in Communities data set with CHD incidence outcomes, two FRSs (FRSv1 from 1998 and FRSv2 from National Cholesterol Education Program Adult Treatment Panel III), along with an additional risk score in which the high density lipoprotein (HDL) component of FRSv1 was ignored (FRSHDL), were compared with a new CHD model (NEW-CHD). This new model contains seven elements: the original Framingham equation, FRSv1, and six additional risk factors. Discrimination, calibration, and reclassification improvements all were assessed among models. RESULTS: Discrimination was improved for NEW-CHD in both cohorts when compared with FRSv1 and FRSv2 (P<0.05) and was similar in magnitude to the improvement of FRSv1 over FRSHDL. NEW-CHD had a similar calibration to FRSv2 and was improved over FRSv1. Net reclassification for NEW-CHD was substantially improved over both FRSv1 and FRSv2, for both cohorts, and was similar in magnitude to the improvement of FRSv1 over FRSHDL. CONCLUSION: While overcoming several methodology deficiencies reported by earlier authors, the NEW-CHD model improved CHD risk assessment when compared with the FRSs, comparable to the improvement of adding HDL to the FRS.

Healthy Eating Index 2005 and selected macronutrients are correlated with improved lung function in humans.

A number of dietary components have been associated with lung function. However, a comprehensive measure of a healthy diet has not been compared with lung function. Herein, we test the hypothesis that a healthy overall diet, as assessed by the Healthy Eating Index 2005 (HEI-2005), will be associated with increased lung function. This is an investigation using the Atherosclerosis Risk in Communities Research Materials obtained from the National Heart Lung Blood Institute. The study surveyed dietary habits of 15 567 American subjects from 4 communities in 1987 to 1990. Spirometric measures of lung function were also taken at entry to the study and a second time 3 years later. Based on food and nutritional data collected by food frequency questionnaire, an HEI-2005 score was calculated for each subject. This total score, together with its 12 components scores and associated macronutrient, was compared with lung function results by linear regression. Models were controlled for smoking behavior, demographics, and other important covariates. The HEI-2005 total scores were positively associated with forced expiratory volume in 1 second per forced vital capacity (FEV(1)/FVC) at visit 1 (ß = .101 per increase in 1 quintile of HEI-2005) and visit 2 (ß = .140), and FEV(1) as percentage of the predicted FEV(1) at visit 2 (ß = .215) (P < .05). In addition, HEI-2005 component scores that represented high intakes of whole grains (ß = .127 and .096); saturated fats (ß = -.091); and solid fats, alcohol, and added sugar (ß = -.109 and -.131) were significantly associated with FEV(1)/FVC at either visit 1 or visit 2. Intakes of total calories (ß =-.082 at visit 1) and saturated fatty acids (ß = -.085 at visit 2) were negatively associated with FEV(1)/FVC. Dietary polyunsaturated fatty acids (ß = .085 and .116) and long-chain omega-3 fatty acids (ß = .109 and .103), animal protein (ß = .132 and .093), and dietary fiber (ß = .129) were positively associated with lung health. An overall healthy diet is associated with higher lung function.

Combined fruit and vegetable intake is correlated with improved inflammatory and oxidant status from a cross-sectional study in a community setting.

Previous studies have examined the relationship between specific nutrient and food intakes with limited markers of either inflammation or oxidant status. The objective of this study was to determine if an increase in combined self-reported fruit and vegetable (F&V) intake in a community setting was associated with improved multiple markers of inflammatory and oxidant status. A community group (N = 1000, age 18-85 years, 61% female) gave two fasted blood samples separated by 12 weeks. Blood inflammatory biomarkers included total leukocytes (WBC), plasma C-reactive protein (CRP), interleukin-6 (IL-6), IL-10, tumor necrosis factor-alpha (TNF-α), monocyte chemoattractant protein-1, and granulocyte colony stimulating factor. Measured oxidant status markers were ferric reducing ability of plasma (FRAP), oxygen radical absorbance capacity (ORAC) and plasma F2-isoprostanes. The relation of markers across categories of F&V intake was examined. In analyses controlling for other important dietary and lifestyle factors, IL-6 and TNF-α were significantly lower across categories of increasing F&V intakes (p < 0.008). FRAP and ORAC were significantly higher (p < 0.0001 and p = 0.047 respectively) while F(2)-isoprostanes was significantly lower (p < 0.0001) across F&V categories. In a community study, several markers of both inflammation and oxidant status were associated in a putatively salutary direction by higher intake of combined F&V, supporting current guidelines suggesting increased F&V consumption for the prevention of chronic diseases.

Synthesis analysis of regression models with a continuous outcome.

To estimate the multivariate regression model from multiple individual studies, it would be challenging to obtain results if the input from individual studies only provide univariate or incomplete multivariate regression information. Samsa et al. (J. Biomed. Biotechnol. 2005; 2:113-123) proposed a simple method to combine coefficients from univariate linear regression models into a multivariate linear regression model, a method known as synthesis analysis. However, the validity of this method relies on the normality assumption of the data, and it does not provide variance estimates. In this paper we propose a new synthesis method that improves on the existing synthesis method by eliminating the normality assumption, reducing bias, and allowing for the variance estimation of the estimated parameters.

Building prediction models for coronary heart disease by synthesizing multiple longitudinal research findings.

BACKGROUND: No methodology is currently available to allow the combining of individual risk factor information derived from different longitudinal studies for a chronic disease in a multivariate fashion. This paper introduces such a methodology, named Synthesis Analysis, which is essentially a multivariate meta-analytic technique. DESIGN: The construction and validation of statistical models using available data sets. METHODS AND RESULTS: Two analyses are presented. (1) With the same data, Synthesis Analysis produced a similar prediction model to the conventional regression approach when using the same risk variables. Synthesis Analysis produced better prediction models when additional risk variables were added. (2) A four-variable empirical logistic model for death from coronary heart disease was developed with data from the Framingham Heart Study. A synthesized prediction model with five new variables added to this empirical model was developed using Synthesis Analysis and literature information. This model was then compared with the four-variable empirical model using the first National Health and Nutrition Examination Survey (NHANES I) Epidemiologic Follow-up Study data set. The synthesized model had significantly improved predictive power (chi = 43.8, P<0.00001). CONCLUSIONS: Synthesis Analysis provides a new means of developing complex disease predictive models from the medical literature.

Combining information from multiple data sources to create multivariable risk models: illustration and preliminary assessment of a new method.

A common practice of metanalysis is combining the results of numerous studies on the effects of a risk factor on a disease outcome. If several of these composite relative risks are estimated from the medical literature for a specific disease, they cannot be combined in a multivariate risk model, as is often done in individual studies, because methods are not available to overcome the issues of risk factor colinearity and heterogeneity of the different cohorts. We propose a solution to these problems for general linear regression of continuous outcomes using a simple example of combining two independent variables from two sources in estimating a joint outcome. We demonstrate that when explicitly modifying the underlying data characteristics (correlation coefficients, standard deviations, and univariate betas) over a wide range, the predicted outcomes remain reasonable estimates of empirically derived outcomes (gold standard). This method shows the most promise in situations where the primary interest is in generating predicted values as when identifying a high-risk group of individuals. The resulting partial regression coefficients are less robust than the predicted values.