Association of a healthy beverage score with total mortality in the adult population of Spain: A nationwide cohort study.

BACKGROUND: Despite the substantial evidence of the relationship between diet and mortality, the role of beverage consumption patterns is not well known. The aim of this study was to assess the association of the adherence to a Healthy Beverage Score (HBS) and all-cause mortality in a representative sample of the Spanish adult population. METHODS AND FINDINGS: We conducted an observational cohort study using data from the Study on Nutrition and Cardiovascular Risk in Spain (ENRICA), which included 12,161 community-dwelling individuals aged ≥18 years recruited in 2008 to 2010 and followed until January 2022. At baseline, food consumption was collected using a validated diet history. The HBS consists of 7 items, each of which is scored from 1 to 4 (highest adherence). The HBS ranges from 7 to 28 points with a higher score representing a healthier pattern. Adherence was assigned as a higher consumption of low-fat milk, and coffee and tea, a lower consumption of whole-fat milk, no consumption of fruit juice, artificially sweetened beverages, or sugar-sweetened beverages, and no or moderate consumption of alcohol. Total mortality was ascertained by linkage to the Spanish National Death Index. Statistical analyses were performed with Cox models and adjusted for the main confounders, including sociodemographic, lifestyle, dietary variables, and morbidity. After a mean follow-up of 12.5 years (SD: 1.7; range: 0.5 to 12.9), a total of 967 deaths occurred. For all-cause mortality, the fully adjusted hazard ratio (HR) for the highest versus lowest sex-specific quartiles of HBS was 0.72 (95% confidence interval [0.57, 0.91], p linear-trend = 0.015), corresponding to an 8.3% reduction in the absolute risk of death. A linear relationship between the risk of death and the adherence to the HBS was observed using restricted cubic splines. The results were robust to sensitivity analyses. The main limitation was that repeated measurements on beverage consumption were not available and beverage consumption could have changed during follow-up. CONCLUSIONS: In this study, we observed that higher adherence to the HBS was associated with lower total mortality. Adherence to a healthy beverage pattern could play a role in the prevention of premature mortality.

Contribution of APOE Genetic Variants to Dyslipidemia.

BACKGROUND: apo (apolipoprotein) E has crucial role in lipid metabolism. The genetic variation in APOE gene is associated with monogenic disorders and contributes to polygenic hypercholesterolemia and to interindividual variability in cholesterol. APOE rare variants may be involved in the phenotype of genetic hyperlipidemias. METHODS: Exon 4 of APOE were sequenced in all consecutive unrelated subjects with primary hyperlipidemia from a Lipid Unit (n=3667) and 822 random subjects from the Aragon Workers Health Study. Binding affinity of VLDL (very low-density lipoprotein) to LDL receptor of pathogenic predicted apoE variants was analyzed in vitro. Lipoprotein particle number, size, and composition were studied by nuclear magnetic resonance. RESULTS: In addition to common polymorphisms giving rise to APOE2 and APOE4, 14 gene variants were found in exon 4 of APOE in 65 subjects. p.(Leu167del) in 8 patients with isolated hypercholesterolemia and in 8 patients with combined hyperlipidemia. Subjects with p.(Arg121Trp), p.(Gly145Asp), p.(Arg154Ser), p.(Arg163Cys), p.(Arg165Trp), and p.(Arg168His) variants met dysbetalipoproteinemia lipid criteria and were confirmed by nuclear magnetic resonance. VLDL affinity for the LDL receptor of p.(Arg163Cys) and p.(Arg165Trp) heterozygous carriers had intermedium affinity between APOE2/2 and APOE3/3. p.(Gly145Asp) and p.(Pro220Leu) variants had higher affinity than APOE3/3. CONCLUSIONS: APOE genetic variation contributes to the development of combined hyperlipidemia, usually dysbetalipoproteinemia, and familial hypercholesterolemia. The lipid phenotype in heterozygous for dysbetalipoproteinemia-associated mutations is milder than the homozygous APOE2/2-associated phenotype. Subjects with dysbetalipoproteinemia and absence of APOE2/2 are good candidates for the study of pathogenic variants in APOE. However, more investigation is required to elucidate the significance of rarer variants of apoE.

Toxic Metals and Subclinical Atherosclerosis in Carotid, Femoral, and Coronary Vascular Territories: The Aragon Workers Health Study.

OBJECTIVE: Studies evaluating the association of metals with subclinical atherosclerosis are mostly limited to carotid arteries. We assessed individual and joint associations of nonessential metals exposure with subclinical atherosclerosis in 3 vascular territories. Approach and Results: One thousand eight hundred seventy-three Aragon Workers Health Study participants had urinary determinations of inorganic arsenic species, barium, cadmium, chromium, antimony, titanium, uranium, vanadium, and tungsten. Plaque presence in carotid and femoral arteries was determined by ultrasound. Coronary Agatston calcium score ≥1 was determined by computed tomography scan. Median arsenic, barium, cadmium, chromium, antimony, titanium, uranium, vanadium, and tungsten levels were 1.83, 1.98, 0.27, 1.18, 0.05, 9.8, 0.03, 0.66, and 0.23 µg/g creatinine, respectively. The adjusted odds ratio (95% CI) for subclinical atherosclerosis presence in at least one territory was 1.25 (1.03-1.51) for arsenic, 1.67 (1.22-2.29) for cadmium, and 1.26 (1.04-1.52) for titanium. These associations were driven by arsenic and cadmium in carotid, cadmium and titanium in femoral, and titanium in coronary territories and mostly remained after additional adjustment for the other relevant metals. Titanium, cadmium, and antimony also showed positive associations with alternative definitions of increased coronary calcium. Bayesian Kernel Machine Regression analysis simultaneously evaluating metal associations suggested an interaction between arsenic and the joint cadmium-titanium exposure. CONCLUSIONS: Our results support arsenic and cadmium and identify titanium and potentially antimony as atherosclerosis risk factors. Exposure reduction and mitigation interventions of these metals may decrease cardiovascular risk in individuals without clinical disease.

The intake of flavonoids, stilbenes, and tyrosols, mainly consumed through red wine and virgin olive oil, is associated with lower carotid and femoral subclinical atherosclerosis and coronary calcium.

PURPOSE: It is suggested that polyphenols back the cardiovascular protection offered by the Mediterranean diet. This study evaluates the association of specific types of dietary polyphenols with prevalent subclinical atherosclerosis in middle-aged subjects. METHODS: Ultrasonography and TC were performed on 2318 men from the Aragon Workers Health Study, recruited between 2011 and 2014, to assess the presence of plaques in carotid and femoral arteries and coronary calcium. Polyphenol intake was assessed using a validated semi-quantitative 136-item food frequency questionnaire. The Phenol Explorer database was used to derive polyphenol class intake. Logistic and linear regressions were used to estimate the cross-sectional association of polyphenols intake with femoral and carotid subclinical atherosclerosis and coronary calcium. RESULTS: A higher intake of flavonoids (third vs. first tertile) was associated with a lower risk of both carotid (OR 0.80: CI 95% 0.62-1.02; P trend 0.094) and femoral (0.62: 0.48-0.80, P trend < 0.001) subclinical atherosclerosis. A higher intake of stilbenes was associated with a lower risk of femoral subclinical atherosclerosis (0.62: 0.46-0.83; P trend 0.009) and positive coronary calcium (0.75: 0.55-1.03; P trend 0.131). A higher intake of tyrosols was also associated with a lower risk of positive coronary calcium (0.80: 0.62-1.03; P trend 0.111). The associations remained similar when adjusted for blood lipids and blood pressure. CONCLUSION: Dietary flavonoids, stilbenes, and tyrosols, whose main sources are red wine and virgin olive oil, are associated with lower prevalence of subclinical atherosclerosis in middle-aged subjects.

Olive oil consumption is associated with lower frailty risk: a prospective cohort study of community-dwelling older adults.

BACKGROUND: There is no evidence on the specific beneficial association of the main types of olive oil consumption with frailty. OBJECTIVE: The aim was to assess the relationship between olive oil consumption and incident frailty in community-dwelling older adults. DESIGN: Prospective cohort. SETTING: Participants were recruited in 2008-10 and follow-up through 2013. SUBJECTS: In total, 1,896 older adults aged 60+. METHODS: At baseline, olive oil and other food consumption was collected using a validated dietary history. Incident frailty was defined as having at least three of the following five Fried-based criteria: low physical activity, fatigue, slow walking, muscle weakness and unintentional weight loss. Analyses were performed with logistic regression and adjusted for the major confounders. RESULTS: Over a mean follow-up of 3.5 years, 135 incident frailty cases were identified. The odds ratio (95% confidence interval) of frailty across sex-specific tertiles of total olive oil consumption (12.7, 20 and 30.8 g/day, respectively) were: 1 (ref.), 0.52 (0.32, 0.83) and 0.47 (0.29, 0.78), P trend 0.003. When differentiating by olive oil types, the results held for virgin but did not for common (refined) olive oil. CONCLUSION: The highest total olive oil consumption (~3 tablespoons), especially if virgin, was associated with half the risk of frailty as the lowest consumption (~1 tablespoon) among older adults. This study suggests that virgin olive oil should be the preferent culinary olive oil type for frailty prevention. If confirmed in other settings, small doses of virgin olive oil could be added as a simple geriatric nutritional advice on the prevention of frailty.

APOE Genotypes Modulate Inflammation Independently of Their Effect on Lipid Metabolism.

The association between APOE genotypes and cardiovascular disease (CVD) is partially mediated by LDL-cholesterol concentration but persists after adjusting for lipid levels and other cardiovascular risk factors. Data from the Aragon Workers Health Study (AWHS) (n = 4159) and the Lipid Unit at the Hospital Universitario Miguel Servet (HUMS) (n = 3705) were used to investigate the relationship between C-reactive protein (CRP) levels and APOE genotype. Lipoprotein particle and GlycA concentrations were analyzed in a subsample from AWHS. APOE genotyping was carried out by the Sanger method in both cohorts. APOE4 carriers had significantly lower levels of CRP than APOE3 carriers. Furthermore, APOE4 carriers had cholesterol-enriched LDL particles compared to APOE2 carriers. APOE4 carriers also had higher concentrations of small, medium, and large LDL particles. CRP levels were not associated with lipoprotein particle number, size, or composition. GlycA levels were not associated with APOE genotypes. However, GlycA levels were significantly associated with the size and the amount of cholesterol contained in HDL, VLDL, and LDL particles. APOE genotype influences CRP concentration regardless of lipid profile. APOE2 carriers showed the highest CRP levels, followed by APOE3 and APOE4. A more atherogenic lipid profile, but not inflammatory markers could partly explain the higher CVD risk observed in APOE4 carriers.

High Consumption of Ultra-Processed Food is Associated with Incident Dyslipidemia: A Prospective Study of Older Adults.

BACKGROUND: Ultra-processed food (UPF) consumption has been associated with higher cardiovascular disease (CVD) and mortality risks. OBJECTIVES: The aim of this study was to assess the relationship between UPF consumption and incident dyslipidemia in older adults, where evidence is limited. METHODS: We studied a prospective cohort of 1082 community-dwelling adults in Spain, older than 60 (mean age, 68 ± 6 years old). Participants (52% were women) were recruited between 2008-10 and followed up to 2015. At baseline, food intake data were collected using a validated computerized face-to-face dietary history. UPFs were identified according to the nature and extent of their industrial processing (NOVA classification). Triglycerides, HDL cholesterol, and LDL cholesterol were measured in fasting plasma samples collected at baseline and at follow-up. Statistical analyses were performed with logistic regression adjusted for the main potential confounders. RESULTS: Among those free of corresponding dyslipidemia at baseline, and after a follow-up of between 5 to 7 years, 60 (out of 895) developed incident hypertriglyceridemia (≥150 mg/dL), 112 (out of 878) had low HDL cholesterol (<40 in men/<50 mg/dL in women), and 54 (out of 472) had high LDL cholesterol (>129 mg/dL). The mean percentage of UPF consumption was 19% ± 11% of total energy intake. Those in the highest versus the lowest tertile of energy intake from UPFs had more than twice the odds of incident hypertriglyceridemia (OR, 2.66; 95% CI: 1.20-5.90; P-trend, 0.011) or low HDL cholesterol (OR, 2.23; 95% CI: 1.22-4.05; P-trend, 0.012). UPF consumption was not associated with high LDL cholesterol plasma concentrations. CONCLUSIONS: Although UPF consumption in Spain was low among older adults, high consumption of UPFs was clearly associated with incident dyslipidemia. The increase in CVD risk recently found to be associated with UPF consumption might be mediated by these atherogenic lipid abnormalities.

High consumption of ultra-processed food may double the risk of subclinical coronary atherosclerosis: the Aragon Workers' Health Study (AWHS).

BACKGROUND: Ultra-processed food (UPF) consumption, which is increasing worldwide, has recently been associated with an increased risk of death and cardiovascular disease. We aimed to assess whether consumption of UPF is directly associated with subclinical coronary atherosclerosis in middle-aged men. METHODS: A computed tomography scan was performed on 1876 men from the Aragon Workers' Health Study, recruited from January 2011 to December 2014, to assess coronary calcium. All participants were free of coronary heart disease. Dietary intake was collected by a validated 136-item semi-quantitative food frequency questionnaire. UPF was defined according to the NOVA classification. Associations between consumption of total energy-adjusted UPF and Coronary Calcium Agatston Score (CACS)-categorized into CACS of 0, > 0 and < 100, and ≥ 100-were cross-sectionally assessed by generalized ordered logistic regression adjusted for main confounders. RESULTS: No coronary calcium was detected in 60.2% of the participants, whereas 10.2% had a CACS ≥ 100. A significant dose-response association was observed between energy-adjusted UPF consumption and the risk of having a CACS ≥ 100, when compared with those in the lowest CACS categories (CACS of 0 together with CACS > 0 and < 100). The fully adjusted ORs (95% CI) of having a CACS ≥ 100 across quartiles of energy-adjusted UPF consumption (approximately 100 g/day in the lowest quartile (ref.) and 500 g/day in the highest) were 1.00 (ref.), 1.50 (0.93, 2.42), 1.56 (0.96, 2.52), and 2.00 (1.26, 3.16), p trend .005. CONCLUSION: In this middle-aged worker's sample, approximately 500 g/day of UPF consumption was associated with a 2-fold greater prevalence of subclinical coronary atherosclerosis than consuming only 100 g/day, independently of total energy intake and other well-established cardiovascular risk factors.

Design and development of an instrument to measure overall lifestyle habits for epidemiological research: the Mediterranean Lifestyle (MEDLIFE) index.

OBJECTIVE: To design and develop a questionnaire that can account for an individual's adherence to a Mediterranean lifestyle including the assessment of diet and physical activity patterns, as well as social interaction. DESIGN: The Mediterranean Lifestyle (MEDLIFE) index was created based on the current Spanish Mediterranean food guide pyramid. MEDLIFE is a twenty-eight-item derived index consisting of questions about food consumption (fifteen items), traditional Mediterranean dietary habits (seven items) and physical activity, rest and social interaction habits (six items). Linear regression models and Spearman rank correlation were fitted to assess content validity and internal consistency. SETTING: A subset of participants in the Aragon Workers' Health Study cohort (Zaragoza, Spain) provided the data for development of MEDLIFE. SUBJECTS: Participants (n 988) of the Aragon Workers' Health Study cohort in Spain. RESULTS: Mean MEDLIFE score was 11·3 (sd 2·6; range: 0-28), and the quintile distribution of MEDLIFE score showed a significant association with each of the individual items as well as with specific nutrients and lifestyle indicators (intra-validity). We also quantified MEDLIFE correspondence with previously reported diet quality indices and found significant correlations (ρ range: 0·44-0·53; P<0·001) for the Alternate Healthy Eating Index, the Alternate Mediterranean Diet Index and Mediterranean Diet Adherence Screener. CONCLUSIONS: MEDLIFE is the first index to include an overall assessment of lifestyle habits. It is expected to be a more holistic tool to measure adherence to the Mediterranean lifestyle in epidemiological studies.

Phthalate exposure and subclinical carotid atherosclerosis: A systematic review and meta-analysis.

Phthalates may be associated with an increased risk of cardiometabolic diseases by interfering with glucose and lipid metabolism and by promoting adipogenesis. This study aimed to perform a systematic review and meta-analysis of the association between phthalate exposure and subclinical carotid atherosclerosis, using surrogate markers such as carotid intima-media thickness (IMT) and carotid plaques. The literature search was performed using four databases (Web of Science, Medline, PubMed, and Scopus), and this systematic review includes all available observational studies until July 6th, 2023. The Joanna Briggs Institute critical appraisal tool was used to assess the risk of bias. Meta-analyses were performed, and random effects models were used. Six high-quality cross-sectional studies and 2570 participants aged 12 to 70 were included. Six phthalate metabolites showed significant associations with subclinical carotid atherosclerosis. Exposure to MBzP, ΣDEHP, and MnBP was associated with increased carotid IMT. Exposure to MEP was associated with a higher prevalence of carotid plaques, and MiBP was associated with a lower prevalence. Mixed results were observed for MMP in older adults. The meta-analyses showed a high degree of heterogeneity, and the results are based on single studies. This study accurately describes the evidence of this association to date, suggesting that phthalates are associated with increased carotid IMT and a higher prevalence of carotid plaques. Further research is needed to elucidate this association, as phthalates are still used in the manufacture of everyday products, humans continue to be exposed to them, and atherosclerosis is a public health concern.

High Serum Phosphate Is Associated with Cardiovascular Mortality and Subclinical Coronary Atherosclerosis: Systematic Review and Meta-Analysis.

(1) Background: Cardiovascular diseases (CVDs) are the leading cause of mortality worldwide. The aim of the study was to examine the existing published results of the association between elevated serum phosphate concentrations and cardiovascular mortality, along with the CVD incidence and subclinical coronary atherosclerosis, in primary prevention among non-selected samples of the general population. (2) Methods: A systematic review and meta-analysis were carried out using literature obtained from PubMed, SCOPUS, and the Web Of Science until March 2024 and following the PRISMA guidelines. Relevant information was extracted and presented. Random and fixed effects models were used to estimate the pooled odds ratio (OR) and hazard ratio (HR) with their 95% coefficient interval (CI), and I2 was used to assess heterogeneity. (3) Results: Twenty-five studies met our inclusion criteria and were included in the meta-analysis (11 cross-sectional and 14 cohort studies). For cardiovascular mortality, which included 7 cohort studies and 41,764 adults, the pooled HR was 1.44 (95% CIs 1.28, 1.61; I2 0%) when the highest versus the reference level of serum phosphate concentrations were compared. For CVDs, which included 8 cohort studies and 61,723 adults, the pooled HR was 1.12 (95% CIs 0.99, 1.27; I2 51%). For subclinical coronary atherosclerosis, which included 11 cross-sectional studies and 24,820 adults, the pooled OR was 1.44 (95% CIs 1.15, 1.79; I2 88%). (4) Conclusions: The highest serum phosphate concentrations were positively associated with a 44% increased risk of cardiovascular mortality and subclinical coronary atherosclerosis.

Association between Sugar-Sweetened Beverage Consumption and the Risk of the Metabolic Syndrome: A Systematic Review and Meta-Analysis.

(1) Background: The increasing occurrence of the metabolic syndrome (MetS) is largely related to harmful food habits. Among them, the consumption of sugar-sweetened beverages (SSBs) is noteworthy. However, to our knowledge, there are not enough high-quality methodological studies summarizing the association between the intake of SSBs and the MetS. Therefore, the aim of this study is to examine the existing published results on this association among adults by synthesizing the existing evidence. (2) Methods: Systematic review and meta-analysis of observational studies following the PRISMA guidelines. Relevant information was extracted and presented following the PRISMA recommendations. PubMed and SCOPUS databases were searched for studies published until June 2022 that assessed the association between SSB consumption (including soft drinks, bottled fruit juices, energy drinks, and milkshakes) and the occurrence of MetS. Random effect models were used to estimate pooled odds ratios (ORs) with their 95% coefficient interval, and I2 was used to assess heterogeneity. (3) Results: A total of 14 publications from 6 different countries were included in this meta-analysis (9 cross-sectional and 5 cohort studies). For the cross-sectional studies, which included 62,693 adults, the pooled OR for the risk of MetS was 1.35 (95% CI 1.15, 1.58; I2 57%) when the highest versus the lowest categories of SSB consumption were compared. For the cohort studies, which included 28,932 adults, the pooled OR was 1.18 (95% CI 1.06, 1.32; I2 70%). (4) Conclusions: The consumption of SSBs was positively associated with an increased risk of MetS. The published literature supports public health strategies and the need to reduce the consumption of SSBs to prevent MetS.

Phthalate exposure and the metabolic syndrome: A systematic review and meta-analysis.

Phthalates are chemicals widely used in plastic-based consumer products, and human exposure is universal. They are classified as endocrine disruptors, and specific phthalate metabolites have been associated with an increased risk of cardiometabolic diseases. The aim of this study was to assess the association between phthalate exposure and the metabolic syndrome in the general population. A comprehensive literature search was performed in four databases (Web of Science, Medline, PubMed, and Scopus). We included all the observational studies that evaluate the association between phthalate metabolites and the metabolic syndrome available until January 31st, 2023. Pooled Odds Ratios (OR) and their 95% confidence intervals were calculated by using the inverse-variance weighted method. Nine cross-sectional studies and 25,365 participants aged from 12 to 80 were included. Comparing extreme categories of phthalate exposure, the pooled ORs for the metabolic syndrome were: 1.08 (95% CI, 1.02-1.16, I2 = 28%) for low molecular weight phthalates, and 1.11 (95% CI, 1.07-1.16, I2 = 7%) for high molecular weight phthalates. For individual phthalate metabolites, the pooled ORs that achieved statistical significance were: 1.13 (95% CI, 1.00-1.27, I2 = 24%) for MiBP; 1.89 (95% CI, 1.17-3.07, I2 = 15%) for MMP in men; 1.12 (95% CI, 1.00-1.25, I2 = 22%) for MCOP; 1.09 (95% CI, 0.99-1.20, I2 = 0%) for MCPP; 1.16 (95% CI, 1.05-1.28, I2 = 6%) for MBzP; and 1.16 (95% CI, 1.09-1.24, I2 = 14%) for DEHP (including ΣDEHP and its metabolites). In conclusion, both low molecular weight and high molecular weight phthalates were associated with an 8 and 11% higher prevalence of the MetS, respectively. The exposure to six specific phthalate metabolites was associated with a higher prevalence of the MetS.

Association of beverage consumption with subclinical atherosclerosis in a Spanish working population.

Beverages play a substantial role meeting water, calorie, and nutrient requirements; however, they are presented as being major contributors to the current obesity epidemic. Although, the relationship between beverage consumption and metabolic risk factors for cardiovascular disease (CVD) in adults has been frequently studied, its association with subclinical atherosclerosis is of increased interest. We studied the association of beverage consumption with the presence of peripheral subclinical atherosclerosis among Spanish workers. We performed a cross-sectional study of 2089 middle-aged males, with a mean age of 50.9 (SD 3.9), and without CVD, carried out in the Aragon Workers' Health Study (AWHS). A food frequency questionnaire was used to measure beverage consumption of low-fat milk, coffee and tea (unsweetened), whole-fat milk, sugar-sweetened beverages, bottled fruit juice, artificially-sweetened beverages and 100% fruit juice. Atherosclerotic plaques were measured by ultrasound (in carotid arteries, and in femoral arteries). Atherosclerotic plaque was defined as a focal structure protruding ≥ 0.5 mm into the lumen, or reaching a thickness ≥ 50% of the surrounding intima-media thickness. As statistical analysis, we use logistic regression models, simultaneously adjusted for all beverage groups. As results, unsweetened coffee was the beverage most associated with peripheral subclinical atherosclerosis with an odds ratio (OR) of 1.25 (1.10-1.41), and 1.23 (1.09-1.40) 100g/day] for carotid, and femoral territories respectively. Moreover, subclinical atherosclerosis was positively associated with whole-fat milk [OR 1.10 (1.02-1.18) 100 g/day] in the femoral territory. The association was protective for low-fat milk in the carotid territory [OR 0.93 (0.88-0.99) 100g/day]. There was also a protective association with bottled fruit juices in the femoral territory [0.84 (0.74-0.94) 100g/day]. Our results suggest a detrimental association with the consumption of coffee, as well as with whole-fat milk and the presence of subclinical atherosclerosis. Therefore, an element of prudence excluding water and low-fat milk, must be applied when recommending beverage consumption.

Polyphenol intake and mortality: A nationwide cohort study in the adult population of Spain.

BACKGROUND AND AIMS: Polyphenols are secondary metabolites present in small quantities in plant-based food and beverages, with antioxidant and anti-inflammatory properties. Main groups of polyphenols include flavonoids, phenolic acids, stilbenes, and lignans, but their association with mortality has barely been examined. We aimed to assess the association between the intake of 23 polyphenol subgroups and all-cause, cardiovascular, and cancer mortality in a representative sample of the Spanish adult population. METHODS: Population-based cohort study conducted with 12,161 individuals aged 18+ recruited in 2008-2010 and followed-up during a mean of 12.5 years. At baseline, food consumption was obtained with a validated dietary history, and the Phenol-Explorer database was used to estimate polyphenol intake. Associations were examined using Cox regression adjusted for main confounders. RESULTS: During follow-up, 967 all-cause deaths occurred, 219 were cardiovascular, and 277 cancer. Comparing extreme categories of consumption, hazard ratios (95% CI) of total mortality for subgroups were: dihydroflavonols 0.85 (0.72-1.00; p-trend:0.046); flavonols 0.79 (0.63-0.97; p-trend:0.04); methoxyphenols 0.75 (0.59-0.94; p-trend:0.021); tyrosols 0.80 (0.65-0.98; p-trend:0.044); alkylmethoxyphenols 0.74 (0.59-0.93; p-trend:0.007); hydroxycinnamic acids 0.79 (0.64-0.98; p-trend:0.014); and hydroxyphenilacetic acids 0.82 (0.67-0.99; p-trend:0.064). For cardiovascular mortality, hazard ratios were: methoxyphenols 0.58 (0.38-0.89; p-trend:0.010); alkylmethoxyphenols 0.59 (0.39-0.90; p-trend:0.011); hydroxycinnamic acids 0.63 (0.42-0.94; p-trend:0.020); and hydroxyphenilacetic acids 0.69 (0.48-0.99; p-trend:0.044), when comparing extreme tertiles of consumption. No statistically significant associations were observed for cancer. The main food sources for these polyphenol subgroups were red wine, leafy green vegetables, olive oil, green olives, and coffee (the latter being the major contributor of methoxyphenols, alkylmethoxyphenols, and hydroxycinnamic acids). CONCLUSIONS: In the Spanish adult population, intake of specific polyphenol subgroups was prospectively associated with a 20% lower all-cause mortality risk. This decrease was mainly due to a 40% lower cardiovascular mortality risk over time.

Low-Quality Carbohydrate Intake Is Associated With a Higher Prevalence of Metabolic Syndrome: The AWHS Study.

CONTEXT: The relationship between carbohydrate quality intake and metabolic syndrome (MetS) is of growing interest. OBJECTIVE: We aimed to assess the association between the adherence to a dietary carbohydrate quality index (CQI) with the occurrence of MetS in a Spanish cohort of working adults. METHODS: A cross-sectional study was conducted of 2316 middle-aged men, aged 50.9 (SD 3.9) years, with no previous cardiovascular disease, and pertaining to the Aragon Workers' Health Study (AWHS) cohort. Diet was collected with a 136-item semiquantitative food-frequency questionnaire. The CQI (range 4-15) was based on: dietary fiber intake, a low glycemic index, the ratio of whole grains/total grains, and the ratio of solid carbohydrates/total carbohydrates. The higher the CQI, the healthier the diet. MetS was defined by using the harmonized National Cholesterol Education Programme-Adult Treatment Panel III (NCEP-ATP III) definition. The associations across 3-point categories of the CQI and the presence of MetS were examined using logistic regression. RESULTS: An inverse and significant association between the CQI and MetS was found. Fully adjusted odds ratios (ORs) for MetS risk among participants in the 10- to 12-point category (second highest CQI category) was 0.64 (95% CI, 0.45-0.94), and in the 13- to 15-point category (highest category) was 0.52 (95% CI, 0.30-0.88), when compared with the 4- to 6-point category (lowest category). Participants with 10 to 12 and 13 to 15 points on the CQI showed a lower risk of hypertriglyceridemia: OR 0.61 (95% CI, 0.46-0.81), and 0.48 (95% CI, 0.32-0.71) respectively. CONCLUSION: Among middle-aged men, a higher adherence to a high-quality carbohydrate diet is associated with a lower prevalence of MetS. Triglyceridemia is the MetS component that contributed the most to this reduced risk.

Association of single and joint metals with albuminuria and estimated glomerular filtration longitudinal change in middle-aged adults from Spain: The Aragon workers health study.

The nephrotoxicity of low-chronic metal exposures is unclear, especially considering several metals simultaneously. We assessed the individual and joint association of metals with longitudinal change in renal endpoints in Aragon Workers Health Study participants with available measures of essential (cobalt [Co], copper [Cu], molybdenum [Mo] and zinc [Zn]) and non-essential (As, barium [Ba], Cd, chromium [Cr], antimony [Sb], titanium [Ti], uranium [U], vanadium [V] and tungsten [W]) urine metals and albumin-to-creatinine ratio (ACR) (N = 707) and estimated glomerular filtration rate (eGFR) (N = 1493) change. Median levels were 0.24, 7.0, 18.6, 295, 3.1, 1.9, 0.28, 1.16, 9.7, 0.66, 0.22 µg/g for Co, Cu, Mo, Zn, As, Ba, Cd, Cr, Sb, Ti, V and W, respectively, and 52.5 and 27.2 ng/g for Sb and U, respectively. In single metal analysis, higher As, Cr and W concentrations were associated with increasing ACR annual change. Higher Zn, As and Cr concentrations were associated with decreasing eGFR annual change. The shape of the longitudinal dose-responses, however, was compatible with a nephrotoxic role for all metals, both in ACR and eGFR models. In joint metal analysis, both higher mixtures of Cu-Zn-As-Ba-Ti-U-V-W and Co-Cd-Cr-Sb-V-W showed associations with increasing ACR and decreasing eGFR annual change. As and Cr were main drivers of the ACR change joint metal association. For the eGFR change joint metal association, while Zn and Cr were main drivers, other metals also contributed substantially. We identified potential interactions for As, Zn and W by other metals with ACR change, but not with eGFR change. Our findings support that Zn, As, Cr and W and suggestively other metals, are nephrotoxic at relatively low exposure levels. Metal exposure reduction and mitigation interventions may improve prevention and decrease the burden of renal disease in the population.

An elevated parametric thyroid feedback quantile-based index is associated with atrial fibrillation.

Introduction: Atrial fibrillation is associated with hyperthyroidism. Within the euthyroid range, it is also associated with high thyroxine (fT4), but not with thyrotropin (TSH). We aim to describe differences in thyroid regulation, measured by the Parametric Thyroid Feedback Quantile-Based Index (PTFQI), between patients with atrial fibrillation and the general population. Materials and methods: Thyroid parameters (PTFQI, TSH, and fT4) of a sample of 84 euthyroid subjects with atrial fibrillation (cases) were compared to a reference sample of euthyroid healthcare patients (controls). We calculated age and sex adjusted ORs for atrial fibrillation across tertiles of these parameters. Also, within cases, we studied thyroid parameters association with clinical characteristics of the atrial fibrillation. Results: After adjusting for age and sex, fT4 and PTFQI were higher in subjects with atrial fibrillation when compared to the general sample (p<0.01 and p=0.01, respectively). Atrial fibrillation ORs of the third versus the first PTFQI tertile was 1.88(95%CI 1.07,3.42), and there was a gradient across tertiles (p trend=0.02). Among atrial fibrillation patients, we observed that higher PTFQI was associated with sleep apnea/hypopnea syndrome (OSAS) (p=0.03), higher fT4 was associated with the presence of an arrhythmogenic trigger (p=0.02) and with heart failure (p<0.01), and higher TSH was also associated with OSAS (p<0.01). Conclusions: Euthyroid subjects with atrial fibrillation have an elevation of the pituitary TSH-inhibition threshold, measured by PTFQI, with respect to the general population. Within atrial fibrillation patients, high PTFQI was associated with OSAS, and high fT4 with heart failure. These results hint of the existence of a relationship between thyroid regulation and atrial fibrillation.

Absence of the influence of the APOE gene on the incidence of type 2 diabetes mellitus in a cohort of workers: Effect of diet and shift work.

BACKGROUND: APOE gene encoded a multifunctional protein in lipid metabolism, also associated with inflammatory markers. Type 2 diabetes (T2D) is a complex metabolic disease related to increased blood glucose, triglycerides and VLDL and associated with different dyslipidaemias. The aim of this study was to analyze whether the APOE genotype could determining the risk of developing T2D in a large cohort of workers. MATERIAL AND METHODS: Data from the Aragon Workers Health Study (AWHS) (n=4895) were used to investigate the relationship between glycemic levels and APOE genotype. All patients in the AWHS cohort had their blood drawn after an overnight fast and laboratory tests were performed on the same day as the blood drawn. Dietary and physical assessment was assessed by face-to-face interview. APOE genotype was determined by the Sanger sequencing method. RESULTS: The relationship between APOE genotype and glycemic profile showed that glucose, Hb1Ac, insulin and HOMA levels did not seem to be associated with the APOE genotype (p=0.563, p=0.605, p=0.333 and p=0.276, respectively). In addition, the T2D prevalence did not show an association with the APOE genotype (p=0.354). Along the same lines, blood glucose levels and T2D prevalence did not show association with the APOE allele. Shift work had some effect on the glycaemic profile, showing that night shift workers have significantly lower levels of glucose, insulin and HOMA (p<0.001). However, the APOE genotype did not show difference in the concentration of glycaemic parameters adjusting by sex, age and BMI, work shift and dietary parameters. CONCLUSION: Glycemic profile and T2D prevalence did not show any significant association with the APOE genotype. Besides, individuals, who worked in non-rotating night shift showed significantly lower glycemic levels, while workers in the morning-afternoon-night shift showed significantly higher values.