High prevalence of non-alcoholic fatty liver disease and metabolic risk factors in Guatemala: A population-based study.

BACKGROUND: There are no data on the prevalence of non-alcoholic fatty liver disease (NAFLD) in general population samples in Guatemala or in other Central American countries. The prevalence and distribution of NAFLD and its associated risk factors were evaluated in a population-based sample of adults in Guatemala. METHODS: Cross-sectional study of 411 men and women 40 years of age or older residing in urban and rural areas of Guatemala. Metabolic outcomes included obesity, central obesity, hypercholesterolemia, diabetes, and metabolic syndrome (MetS). Liver disease outcomes included elevated liver enzymes, elevated Fatty Liver Index (FLI), and elevated FIB-4 score. RESULTS: The overall prevalence of obesity, central obesity, diabetes, and MetS were 30.9, 74.3, 21.6, and 64.2%, respectively. The fully-adjusted prevalence ratios (95% CI) for obesity, central obesity, diabetes, and MetS comparing women to men were 2.83 (1.86-4.30), 1.72 (1.46-2.02), 1.18 (1.03-1.34), and 1.87 (1.53-2.29), respectively. The overall prevalence of elevated liver enzymes (ALT or AST), elevated FLI, and elevated FIB-4 scores were 38.4, 60.1, and 4.1%, respectively. The fully-adjusted prevalence ratios (95% CI) for elevated liver enzymes (either ALT or AST) and elevated FLI score comparing women to men were 2.99 (1.84-4.86) and 1.47 (1.18-1.84), respectively. CONCLUSIONS: The prevalence of metabolic abnormalities and liver outcomes in this general population study was very high. The prevalence of metabolic and liver abnormalities was particularly high among women, an observation that could explain the atypical 1:1 male to female ratio of liver cancer in Guatemala.

Lower-normal TSH is associated with better metabolic risk factors: A cross-sectional study on Spanish men.

BACKGROUND AND AIMS: Subclinical thyroid conditions, defined by normal thyroxin (T4) but abnormal thyroid-stimulating hormone (TSH) levels, may be associated with cardiovascular and metabolic risk. More recently, TSH levels within the normal range have been suggested to be associated with metabolic syndrome and cardiovascular risk. This work studies the linearity of the relationship between metabolic syndrome and TSH across the euthyroid range. METHODS AND RESULTS: We studied 3533 male participants of the Aragon Workers' Health Study (AWHS) with normal TSH and free T4 levels, across quintiles of these variables, after adjusting for age, alcohol intake, and smoking. Compared with the lowest TSH quintile, the odds ratios for metabolic syndrome at the higher quintiles, which indicate lower thyroid function, were 1.34 (1.04, 1.73), 1.56 (1.21, 2.01), 1.57 (1.22, 2.03), and 1.71 (1.32, 2.21). The lowest free T4 quintile also showed an odds ratio of 1.49 (1.16, 1.90) with respect to the highest quintile. In addition, spline models showed departures from linearity: the risk of metabolic syndrome mostly increases at TSH values below the median (sample half-closest to subclinical hyperthyroidism). Interestingly, glucose also increases with TSH primarily below the median TSH, diastolic blood pressure shows similar changes across the entire TSH range, whereas body mass index, triglycerides, and high-density lipoprotein (HDL)-cholesterol change only at the highest normal TSH values, which are associated with lower free T4 concentration. CONCLUSIONS: TSH and free T4 within the normal range are associated with the metabolic syndrome. The sample half-below the TSH median (with probably higher functional thyroid status) exhibited better metabolic and cardiovascular profiles.

Meta-analysis: vitamin D and non-alcoholic fatty liver disease.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a highly prevalent condition. Emerging evidence suggests that vitamin D may play a role in the pathogenesis of NAFLD. AIM: To review systematically the association between vitamin D levels, measured as serum 25-hydroxy vitamin D [25(OH)D], and NAFLD. METHODS: We used PubMed and EMBASE databases to identify all studies that assessed the association between vitamin D and NAFLD up until 22 April 2013, without language restrictions. We included studies that compared vitamin D levels between NAFLD cases and controls and also those that compared the odds of vitamin D deficiency by NAFLD status. Pooled standardised differences and odds ratios were calculated using an inverse variance method. RESULTS: Seventeen cross-sectional and case-control studies have evaluated the association between vitamin D and NAFLD. NAFLD was diagnosed using biopsy (4 studies), ultrasound or CT (10 studies) and liver enzymes (3 studies). Nine studies provided data for a quantitative meta-analysis. Compared to controls, NAFLD patients had 0.36 ng/mL (95% CI: 0.32, 0.40 ng/mL) lower levels of 25(OH)D and were 1.26 times more likely to be vitamin D deficient (OR 1.26, 95% CI: 1.17, 1.35). CONCLUSIONS: NAFLD patients have decreased serum 25(OH)D concentrations, suggesting that vitamin D may play a role in the development of NAFLD. The directionality of this association cannot be determined from cross-sectional studies. Demonstration of a causal role of hypovitaminosis D in NAFLD development in future studies could have important therapeutic implications.

Cardiovascular disease prevention in women: a rapidly evolving scenario.

The past decade has witnessed a long overdue recognition of the importance of CVD in women, accompanied by an increasing awareness of gender differences in risk factors, natural history, preventive strategies, treatment, and prognosis of CVD. Reflecting the disease burden and the specific aspects of CVD in women, the American Heart Association has developed women-specific evidence-based guidelines and consensus documents for CVD prevention. The most recent update of these guidelines, published in 2011, is a milestone in the field and shows the rapidly evolving scenario of CVD prevention in women. We discuss some novel aspects of the 2011 update. The new guidelines change the focus from evidence-based to effectiveness-based, with consideration of both benefits and harms/costs of preventive interventions. The guidelines also introduce "ideal cardiovascular health" as the lowest category of risk, which implies the need of communitywide preventive, educational and policy initiatives to promote healthy lifestyles in the general population. Furthermore, the guidelines emphasize long-term overall CVD risk rather than short-term coronary risk. We also address several barriers and open questions in the evaluation and implementation of these guidelines, including how to increase the small proportion of women with ideal cardiovascular health; how to increase implementation and compliance with the recommendations; how to provide effectiveness-based recommendations for lifetime prevention goals based on short-term trials; how to obtain the best possible evidence in women; how to identify subgroups of women with different cardiovascular risk profiles or who may require tailored preventive strategies; and how to adapt current guidelines to international settings, particularly to low- and middle-income countries.

Structured management strategy based on the Gastro-oesophageal Reflux Disease (GERD) Questionnaire (GerdQ) vs. usual primary care for GERD: pooled analysis of five cluster-randomised European studies.

BACKGROUND: Response to treatment among primary care patients with gastro-oesophageal disease (GERD) is variable. AIM: The GERD Management Project (GMP) evaluated the effectiveness of a structured management approach to GERD vs. standard treatment (usual care). METHODS: Data from five cluster-randomised clinical trials in adult primary care patients with symptoms of GERD were pooled. The structured pathway was based on the self-administered GERD Questionnaire (GerdQ) and was compared with standard treatment. RESULTS: 1734 patients were enrolled (structured treatment, n=834; standard treatment, n=900). The difference in the mean GerdQ score change from baseline favoured the structured pathway (-0.61; 95% CI: -0.88, -0.34; p<0.001). The odds ratio for an indication for treatment revision at the end of follow-up (structured vs. standard treatment) was 0.39 (95% CI: 0.29, 0.52; p=0.001). CONCLUSIONS: Management of primary care patients with GERD can be improved by systematic stratification of patients using a patient management tool such as the GerdQ.

The association of biomarkers of iron status with mortality in US adults.

BACKGROUND AND AIMS: Elevated iron biomarkers are associated with diabetes and other cardiometabolic abnormalities in the general population. It is unclear whether they are associated with an increased risk of all-cause or cause-specific mortality. The purpose of the current analysis was to evaluate the association of ferritin and transferrin saturation levels with all-cause, cardiovascular, and cancer mortality in the general US adult population. METHODS AND RESULTS: A prospective cohort study was conducted with 12,258 adults participating in the Third National Health and Nutrition Examination Survey (NHANES III), a nationally representative sample of the US population. Study participants were recruited in 1988-1994 and followed through December 31, 2006 for all-cause, cardiovascular disease, and cancer mortality. The multivariable-adjusted hazard ratios (95% confidence interval) for all-cause mortality comparing the fourth versus the second quartiles of ferritin and transferrin saturation were 1.09 (0.82-1.44; p-trend across quartiles = 0.92) and 1.08 (0.82-1.43; p-trend across quartiles = 0.62), respectively, for men, 1.43 (0.63-3.23; p-trend across quartiles = 0.31) and 1.48 (0.70-3.11; p-trend across quartiles = 0.60), respectively, for premenopausal women, and 1.03 (0.79-1.34; p-trend across quartiles = 0.95) and 1.17 (0.92-1.49; p-trend across quartiles = 0.63), respectively, for postmenopausal women. Quartile of ferritin and transferrin saturation also showed no association between biomarkers of iron status and mortality. CONCLUSIONS: In a large nationally representative sample of US adults, within the spectrum of normal iron metabolism, ferritin and transferrin saturation were not associated with risk of mortality among people who were not taking iron supplements and did not have a baseline history of cardiovascular disease or cancer.

Selenium status and blood lipids: the cardiovascular risk in Young Finns study.

BACKGROUND: Concern has been recently raised about possible adverse cardio-metabolic effects of high selenium status, such as increased risks of diabetes and hyperlipidaemia. However, most of the evidence comes from selenium-replete populations such as that of the United States. OBJECTIVES: To examine cross-sectional and longitudinal associations of serum selenium with cardiovascular risk factors in Finland where selenium levels were amongst the lowest in the world until the early 1980s before the implementation of a nationwide selenium fertilization programme. METHODS: Serum selenium was measured in 1235 young Finns aged 3-18 years at baseline in 1980 (prefertilization) and in a subgroup (N = 262) at the 6-year follow-up (1986, postfertilization). During the 27-year follow-up, serum lipids, blood pressure, body mass index and smoking were assessed five times (1980, 1983, 1986, 2001 and 2007). RESULTS: Mean (±SD) serum selenium concentrations were 74.3 ± 14.0 ng mL(-1) in 1980 and 106.6 ± 12.5 ng mL(-1) in 1986 (average increase 32.3 ng mL(-1); 95% CI: 30.3 to 34.3, P < 0.0001). In univariate and multivariable cross-sectional models in 1980 and 1986, increased serum selenium levels were consistently associated with increased total, HDL and Low-density lipoprotein (LDL) cholesterol. However, the average longitudinal changes in lipids were -0.20 mmol L(-1) (95% CI: -0.30 to -0.10, P < 0.0001) for total cholesterol, 0.06 mmol L(-1) (95% CI: 0.03 to 0.10, P < 0.0001) for HDL cholesterol, and -0.23 mmol L(-1) (95% CI: -0.31 to -0.14, P < 0.0001) for LDL cholesterol. Selenium measured in 1986 was not associated with lipids assessed in 2001 and 2007. CONCLUSIONS: Cross-sectional findings from the Young Finns study corroborate positive associations of selenium status with serum lipids. However, longitudinal evidence does not support the causality of this link.

Selenium status and cardiometabolic health: state of the evidence.

Use of selenium enriched foods, supplements and fertilizers has increased markedly in recent years in the US and other Western countries because of the perception that the anti-oxidant properties of selenium could potentially reduce the risk of cancer and other chronic diseases. However, concern has been raised recently about possible adverse cardiometabolic effects of high selenium exposure, including an increased risk of diabetes and hyperlipidemia with high selenium intake. Hence, from a public health perspective, the relationship between selenium status and cardiometabolic health should be clarified in order to help guide consumers in their choices of nutritional supplements and enriched food products. Additional experimental evidence is needed to provide new insights into the role of selenium and of specific selenoproteins in human biology, especially to clarify the underlying mechanisms linking selenium to chronic disease endpoints. Further epidemiological studies and randomized clinical trials across populations with different selenium status should be conducted to determine the causal effect of selenium on cardiovascular disease and risk factors. Nevertheless, at the present time the widespread use of selenium supplements or other strategies that artificially increase selenium status above the level required for optimal selenoprotein activity is not justified and should not be encouraged.

Physical activity and white matter lesion progression: assessment using MRI.

We evaluated the association between physical activity and changes in white matter lesions (WMLs) on MRI in a sample of 179 older adults comprising 59 incident cases of Alzheimer disease, 60 persons with mild cognitive impairment, and 60 persons who remained cognitively stable over a median 5-year follow-up. Physical activity was not significantly associated with a decreased rate of periventricular or deep WML progression.

A case-crossover study of fine particulate matter air pollution and onset of congestive heart failure symptom exacerbation leading to hospitalization.

Persons with congestive heart failure may be susceptible to ambient air pollution. The authors evaluated the association between exposure to particulate matter with an aerodynamic diameter of <2.5 microm (PM2.5) and onset of symptom exacerbation leading to hospital admission in Baltimore, Maryland. They used a case-crossover design for 135 case events occurring among 125 persons with prevalent congestive heart failure who were admitted to a single hospital through the emergency department during 2002. The case period was assigned using three index times: 8-hour and 24-hour periods of symptom onset and date of hospital admission. Controlling for weather, the authors detected a modest relative increase in risk for cases defined by 8-hour symptom onset for an interquartile-range increase in PM2.5 at a 2-day lag (odds ratio=1.09, 95% confidence interval: 0.91, 1.30). A corresponding increase in risk was not observed when admission date was used to define the case period. A series of simulations based on study data indicated that the study had adequate statistical power to detect odds ratios of 1.2 or higher. Although overall findings were not statistically significant, the identification of case events defined by an 8-hour onset period may be more relevant than either a 24-hour onset period or the admission date for estimating harmful effects of air pollutant exposure on cardiovascular health.

Relationship between systemic markers of inflammation and serum beta-carotene levels.

BACKGROUND: Low serum levels of beta-carotene have been associated with increased risk of cancer and cardiovascular disease. However, in clinical trials, supplementation of the diet with beta-carotene either had no benefit or caused harm. This pattern of findings raises the possibility that confounding by other factors might explain the association between serum beta-carotene level and disease risk. METHODS: We used data from 14 470 current smokers, ex-smokers, and never smokers aged 18 years or older who participated in the Third National Health and Nutrition Examination Survey to assess the relationship between serum beta-carotene and markers of inflammation (C-reactive protein and white blood cell count). RESULTS: After adjustment for beta-carotene intake and other factors, geometric mean levels of serum beta-carotene for individuals with undetectable (< 0.22 mg/dL), mildly elevated (0.22-0.99 mg/dL), and clinically elevated (> or =1.0 mg/dL) C-reactive protein levels were 18.0, 16.1, and 13.6 microg/dL, respectively, in never smokers; 18.1, 15.7, and 13.9 microg/dL in ex-smokers; and 11.3, 10.2, and 9.4 microg/dL in current smokers (P< .001 for all). In corresponding analyses, white blood cell count was also inversely related to serum beta-carotene concentration (P< .05 for all). CONCLUSIONS: The strong and inverse association of serum beta-carotene level with C-reactive protein level and white blood cell count suggests that the relationship between serum beta-carotene concentration and disease risk might be confounded by inflammation. More broadly, for beta-carotene and likely other nutrients, it seems unwise to interpret biomarker data as prima facie evidence of dietary intake without a more complete understanding of the physiologic processes that affect nutrient levels.

Autologous blood transfusion in the United States: clinical and nonclinical determinants of use.

BACKGROUND: Preoperative donation of blood lowers the risk of allogeneic RBC transfusion. The use of autologous blood is not well quantified. This study aimed at identifying the frequency and determinants of use of autologous transfusion in the United States. STUDY DESIGN AND METHODS: This national cross-sectional study, using the Nationwide Inpatient Sample, included all patients admitted to 900 hospitals in 19 states in 1996. Logistic regression with weighting yielded nationally representative results for the independent effects of clinical and nonclinical patient characteristics on autologous blood use. RESULTS: Autologous transfusion was used in 19 of 1000 hospitalizations. The procedures using autologous blood most frequently were knee arthroplasty, hip replacement, prostatectomy, spinal fusion, and hysterectomy. Blacks and Hispanics were less likely to receive autologous transfusion than were whites (OR, 0. 64; 95% CI, 0.45-0.83); patients with Medicaid were less likely than the privately insured to receive autologous transfusions (OR, 0.29; 95% CI, 0.20-0.43), with racial differences greatest among the privately insured. Women received autologous blood for cardiovascular surgeries much less often than men (OR, 0.32; 95% CI, 0.20-0.49). CONCLUSION: Ethnic minorities, women, and patients with Medicaid appear to receive fewer autologous blood transfusions than the rest of the population. Although this could reflect either better or worse quality of care, nonclinical determinants of transfusion practice warrant attention and further investigation.

Determinants of p,p-dichlorodiphenyldichloroethane (DDE) concentration in adipose tissue in women from five European cities.

To identify the determinants of p,p'-dichlorodiphenyldichloroethane (p,p'-DDE) in adipose tissue in subjects who participated in a cross-sectional study, we analyzed fatty acids, antioxidants, and p,p'-DDE in aspirates of adipose tissue of 328 postmenopausal women from 5 European countries. The overall mean of p,p'-DDE concentration was 1.66 microg/g of fatty acids (95% confidence interval = 1.46, 1.88). In a multiple-regression analysis, the main predictors of log10(p,p'DDE) were center of recruitment (p < .0001), adipose arachidic acid (p = .001), and adipose retinol (p = .04). These factors explained 14.9% of the overall variability of log10(p,p'-DDE). In our subjects, adipose tissue p,p'DDE concentrations were only weakly related with biomarkers reflecting intake of fish and other foods. This result is consistent with the notion that p,p'-DDE exists in different foods and, given the widespread contamination of the food chain, is relatively evenly distributed among foods.

[Nutrition surveys of Spanish school-age children: analysis of the period 1984-1994]. / Encuestas alimentarias en los niños españoles de edad escolar: análisis del período 1984-1994.

OBJECTIVE: To review available data on the usual dietary intake of school-age Spanish children, by analyzing the nutritional surveys carried out during the period 1984-1994. METHODS: Systematic and comprehensive search of surveys with dietary data in Spanish children aged 6 to 16 years collected during the period 1984-1994 and published after January 1997. The search of bibliographic databases (MEDLINE, IME, ISBN and Teseo), was completed with an extensive search of the gray literature and of unpublished studies through contact with public and private institutions which may fund such studies. The quality of the original surveys was assessed, and the data of the studies fulfilling pre-established quality requirements were summarized and tabulated. RESULTS: We located 65 nutritional surveys in children and adolescents performed between 1984 and 1994, which generated 91 documents. Most surveys (76.9%) were local, while 18.5% of them studied provinces or regions and 3.1% studied more than one region. Only 4 studies (6.2%) met the quality requirements, but the methods or the presentation of the results of these surveys were too heterogeneous. In spite of that, the available data tends to show a certain lack of balance of macronutrient intakes in relation to the usual dietary recommendations. CONCLUSIONS: Available data on nutritional intake of Spanish school-age children during 1984-1994 were too heterogeneous to be comparable, even if the analysis was restricted to high-quality surveys. Furthermore, there are no repeated surveys monitoring changes in intake in representative samples of children performed during the study period. This should be taken into account in future research endeavours which should contemplate a well defined sampling framework and the appropriate methodology to assure the proper interpretation of the eventual results.

Cost-benefit analysis of Haemophilus influenzae type b vaccination in children in Spain.

OBJECTIVE: Invasive disease caused by Haemophilus influenzae type b (Hib), including meningitis, pneumonia, sepsis and epiglottitis, is associated with high mortality and serious neurological sequelae in children under 5 years of age. The availability of an efficacious vaccine suggests the need to perform an economic evaluation of its use. The objective of this study was to evaluate the costs and benefits of introducing a universal vaccination programme for children under 1 year of age in Spain. DESIGN & SETTING: A cost-benefit analysis (CBA) was conducted over a 5-year period from the societal perspective in the Spanish healthcare setting. Both direct and indirect costs were included in the analysis [using 1996 Spanish pesetas (Pta); Pta126.5 = $US1 in April 1996]. PATIENTS AND PARTICIPANTS: The target population used for cost and benefit estimation was the 384,883 Spaniards aged 1 year or less in the last Spanish Population and Housing Census of 1991. MAIN OUTCOME MEASURES AND RESULTS: The introduction of the universal Hib vaccination programme would imply vaccinating 346,395 children under 1 year of age, with a global expense of Pta2,444,855,910. For an average incidence of 15 cases of invasive disease per 100,000 children per year nationwide, the programme would prevent 219 cases of invasive disease and 8 deaths over a 5-year period, with a benefit of Pta2,182,868,907, a net benefit (i.e. benefit minus cost) of -Pta261,987,003, a benefit/cost ratio of 0.89 and a benefit per case prevented of -Pta1,196,288. Benefit/cost ratios above 1 would be obtained in the regions of highest incidence of invasive disease. CONCLUSION: The decision to implement a universal vaccination programme should not be based only on economic factors, but our results suggest that the economic returns of the programme for children under 1 year of age in Spain would be at least of a similar magnitude as its expenses.

Omega-3 fatty acids in adipose tissue and risk of myocardial infarction: the EURAMIC study.

Omega-3 fatty acids have potential antiatherogenic, antithrombotic, and antiarrhythmic properties, but their role in coronary heart disease remains controversial. To evaluate the association of omega-3 fatty acids in adipose tissue with the risk of myocardial infarction in men, a case-control study was conducted in eight European countries and Israel. Cases (n=639) included patients with a first myocardial infarction admitted to coronary care units within 24 hours from the onset of symptoms. Controls (n=700) were selected to represent the populations originating the cases. Adipose tissue levels of fatty acids were determined by capillary gas chromatography. The mean (+/-SD) proportion of alpha-linolenic acid was 0.77% (+/-0.19) of fatty acids in cases and 0.80% (+/-0.19) of fatty acids in controls (P=0.01). The relative risk for the highest quintile of alpha-linolenic acid compared with the lowest was 0.42 (95% confidence interval [CI] 0.22 to 0.81, P-trend=0.02). After adjusting for classical risk factors, the relative risk for the highest quintile was 0.68 (95% CI 0.31 to 1.49, P-trend=0.38). The mean proportion of docosahexaenoic acid was 0.24% (+/-0.13) of fatty acids in cases and 0.25% (+/-0.13) of fatty acids in controls (P=0. 14), with no evidence of association with risk of myocardial infarction. In this large case-control study we could not detect a protective effect of docosahexaenoic acid on the risk of myocardial infarction. The protective effect of alpha-linolenic acid was attenuated after adjusting for classical risk factors (mainly smoking), but it deserves further research.

Use of two-segmented logistic regression to estimate change-points in epidemiologic studies.

In many epidemiologic data, the dose-response relation between a continuous exposure and the risk of disease abruptly changes when the exposure variable reaches an unknown threshold level, the so-called change-point. Although several methods are available for dose-response assessment with dichotomous outcomes, none of them provide inferential procedures to estimate change-points. In this paper, we describe a two-segmented logistic regression model, in which the linear term associated with a continuous exposure in standard logistic regression is replaced by a two-segmented polynomial function with unknown change-point, which is also estimated. A modified, iteratively reweighted least squares algorithm is presented to obtain parameter estimates and confidence intervals, and the performance of this model is explored through simulation. Finally, a two-segmented logistic regression model is applied to a case-control study of the association of alcohol intake with the risk of myocardial infarction and compared with alternative analyses. The ability of two-segmented logistic regression to estimate and provide inferences for the location of change-points and for the magnitude of other parameters of effect will make this model a useful complement to other methods of dose-response analysis in epidemiologic studies.