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.

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.

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 / Ausencia de la influencia del gen APOE en la incidencia de diabetes mellitus tipo 2 en una cohorte de trabajadores: efecto de la dieta y la turnicidad laboral

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. (AU)

Introducción: El gen APOE codifica una proteína multifuncional en el metabolismo de los lípidos y asociada con marcadores inflamatorios. La diabetes tipo 2 (T2D) es una enfermedad metabólica compleja relacionada con aumento de glucosa en sangre, triglicéridos y VLDL y asociado a diferentes dislipidemias. El objetivo de este estudio fue analizar si el genotipo APOE podría determinar el riesgo de desarrollar T2D en una gran cohorte de trabajadores. Material y métodos: Se utilizaron datos de la cohorte Aragon Workers Health Study (AWHS) (n = 4895) para investigar la relación entre los niveles glucémicos y el genotipo APOE. Se extrajo una muestra de sangre tras ayuno a todos los trabajadores de la AWHS y se realizaron pruebas de laboratorio el mismo día de la extracción de sangre. La evaluación dietética y física se evaluó mediante una entrevista presencial. El genotipo APOE se determinó por el método de secuenciación Sanger. Resultados: La glucosa, los niveles de Hb1Ac, insulina y HOMA no parecen estar asociados con el genotipo APOE (p = 0.563, p = 0,605, p = 0,333 y p = 0,276, respectivamente). Además, la prevalencia de T2D no mostró una asociación con el genotipo APOE (p = 0,354). Del mismo modo, los niveles de glucosa en sangre y la prevalencia de T2D no mostró asociación con ningún alelo de APOE. El trabajo por turnos tuvo algún efecto en el perfil glucídico, mostrando que los trabajadores del turno de noche tienen niveles significativamente más bajos de glucosa, insulina y HOMA (p < 0,001). Sin embargo, el genotipo APOE no mostró diferencia en la concentración de parámetros glucídicos ajustando por sexo, edad e IMC, jornada laboral y parámetros dietéticos. (AU)

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.

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.

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.

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.

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.

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.

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.

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.

Cardiorespiratory fitness decreases the odds for subclinical carotid plaques in apolipoprotein e4 homozygotes.

Some studies suggest that being an apolipoprotein e4 (APOE e4) carrier increases the risk of atherosclerosis, and others suggest that cardiorespiratory fitness (CRF) could play a key role in atherosclerotic prevention. Our aim was to analyze the association of APOE e4 with carotid atherosclerosis and the association of CRF with atherosclerosis in APOE e4 carriers. A cross-sectional analysis based on a subsample of 90 participants in the Aragon Workers' Health Study was carried out. Ultrasonography was used to assess the presence of plaques in carotid territory; the submaximal Chester Step Test was used to assess CRF; and behavioral, demographic, anthropometric, and clinical data were obtained by trained personnel during annual medical examinations. APOE e4e4 participants were categorized into Low-CRF (VO2max < 35 mL/kg/min) and High-CRF (VO2max ≥ 35 mL/kg/min) groups. After adjusting for several confounders, compared with APOE e3e3, those participants genotyped as APOE e3e4 and APOE e4e4 showed an OR = 1.60 (95% CI 0.45, 5.71) and OR = 4.29 (95% CI 1.16, 15.91), respectively, for carotid atherosclerosis. Compared to Low-CRF APOE e4e4 carriers, the odds of carotid plaque detection were 0.09 (95% CI 0.008, 0.98) times lower among High-CRF APOE e4e4 carriers. The APOE e4e4 genotype was associated with increased carotid atherosclerosis. However, CRF is a modifiable factor that may be targeted by APOE e4e4 to decrease the elevation of atherosclerotic risk due to this genetic condition.

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.

A Cross-Sectional Study Examining the Parametric Thyroid Feedback Quantile Index and Its Relationship with Metabolic and Cardiovascular Diseases.

Background: The usual inverse correlation between thyrotropin (TSH) and thyroid hormone disappears in syndromes of central resistance to thyroid hormone, where both are high. TSH and thyroid hormone are also simultaneously high when there is an elevation of the set point of the thyroid regulation axis. This can be estimated with indices, such as the Parametric Thyroid Feedback Quantile-based Index (PTFQI), which was designed for the general population. The PTFQI is positively associated with diabetes prevalence, but association with other pathologies has not been yet explored. The aim of this project was to explore the potential relationship of the PTFQI with metabolic and cardiovascular disease in a sample of ambulatory adult patients from Spain. Methods: A cross-sectional study was carried out among the patients who underwent thyroid hormones measurement (6434 measurements from September to November 2018 in a central laboratory in Spain). We retrospectively reviewed clinical records of a subgroup of adults aged >18 years with normal TSH and free thyroxine (fT4) belonging to groups that represent extreme PTFQI (n = 661). Individuals with known conditions interfering the thyroid axis were excluded (remaining n = 296). Logistic and linear regression models adjusted for age and sex were used to calculate odds ratio (OR) of diseases and differences of clinical parameters, and 95% confidence intervals [CI]. Results: Across levels with higher PTFQI, there was an increase in the prevalence of type 2 diabetes (High vs. Low PTFQI OR: 2.88 [CI: 1.14-7.86], p-Trend = 0.02), ischemic heart disease (16.4% vs. 0%, unadjusted Haldane-Anscombe corrected OR: 23.90 [CI: 1.36-21.48], adjusted p-Trend = 0.04), atrial fibrillation (OR: 8.13 [CI: 1.33-158.20], p-Trend = 0.05), and hypertension (OR: 3.19 [CI: 1.14-9.94], p-Trend = 0.05). While the prevalence of type 2 diabetes was similarly associated with TSH and fT4, ischemic heart disease, atrial fibrillation, and hypertension were more strongly associated with the differences in fT4 values. Conclusions: Type 2 diabetes, ischemic heart disease, atrial fibrillation, and hypertension may be associated with a higher central regulation set point for thyroid hormone. These findings should be confirmed in other populations.

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.

A cross-sectional analysis of the association between physical activity, depression, and all-cause mortality in Americans over 50 years old.

Depression is estimated to be the second leading cause of disability in the United States and is associated with a 52% increased risk of death. Lifestyle components may have an important role in depression pathogenesis. The aims of this study were to analyze the association of meeting the physical activity (PA) recommendation guidelines and depression, and to analyze the all-cause mortality risk of the joint association of PA and depression. This cross-sectional study included 7201 participants from the 2007-2014 National Health and Nutrition Examination Survey aged ≥ 50 years and linked to National Death Index records through December 31, 2015. Depression was defined as a score ≥ 10 using the Patient Health Questionnaire (PHQ-9). PA was self-reported, and total PA was used to classify participants as more active (≥ 600 MET-min/week) or less active (< 600 MET-min/week). The odds ratios for depression were examined according to be more active or less active. The hazard ratios (HR) for the association of PA level and depression status with all-cause mortality were examined. Being more active was associated with reduced odds for depression. Compared with less active participants with depression, those who were more active and having depression had HR 0.45 (95% CI 0.22, 0.91, p = 0.026) for all-cause mortality. Being more active is associated with lower odds for depression and seems to be a protective factor against the increased all-cause mortality risk due to depression.

Olive oil consumption is associated with a lower risk of cardiovascular disease and stroke.

BACKGROUND & AIMS: The specific association of olive oil consumption with coronary heart disease (CHD) or stroke has not been totally established. OBJECTIVE: to examine whether olive oil consumption is associated with subclinical atherosclerosis, the risk of total cardiovascular disease (CVD), CHD, and stroke. METHODS: Three cohorts were included: AWHS (2318 men), SUN Project (18,266 men and women), and EPIC-Spain (39,393 men and women). Olive oil consumption was measured at baseline using validated questionnaires. RESULTS: In the AWHS, 747 participants had a positive coronary artery calcium score (CACS>0), and the OR (95% CI) was 0.89 (0.72, 1.10) in those with virgin olive oil consumption ≥30 g/day (v. <10 g/day). In the SUN Project (follow-up 10.8 years) 261 total CVD cases occurred, and the HR was 0.57 (0.34, 0.96) for consumptions ≥30 g/day (v. <10 g/day). In the EPIC-Spain (follow-up 22.8 years) 1300 CHD cases and 938 stroke cases occurred; the HRs for stroke according, 0 to <10 (ref), 10 to <20, 20 to <30, and ≥30 g/day of olive oil consumption, were 0.84 (0.70, 1.02), 0.80 (0.66, 0.96), 0.89 (0.74, 1.07). A weaker association was observed for CHD. The association was stronger among those consuming virgin olive oil, instead of common (refined). CONCLUSIONS: Olive oil is associated with lower risk of CVD and stroke. The maximum benefit could be obtained with a consumption between 20 and 30 g/day. The association could be stronger for virgin olive oil and might operate from the early stages of the disease.

Association of physical activity levels and prevalence of major degenerative diseases: Evidence from the national health and nutrition examination survey (NHANES) 1999-2018.

OBJECTIVES: Degenerative diseases are associated with lower healthy life expectancy and higher mortality. Physical activity (PA) has demonstrated a fundamental role in the prevention and control of several pathologies associated to the aging process. The aim of this study was to analyze the association of PA with the prevalence of sarcopenia, osteoporosis and osteoarthritis in non-institutionalized American population. METHODS: Cross-sectional study carried out in participants aged ≥50 years from the 1999-2018 National Health and Nutrition Examination Survey (NHANES). Sarcopenia was defined using appendicular lean mass adjusted for body mass index (ALM:BMI; men <0.789 kg/m2, women <0.512 kg/m2). Osteoporosis was defined as bone mineral density T-score ≤-2.5 of femur neck. Osteoarthritis and PA were self-reported, and total PA was used to classify participants in groups. The Odds Ratios among the different PA levels for each disease were examined. RESULTS: Performing at least 150 MET-min/week of PA was associated with reduced odds for sarcopenia; performing >1800 MET-min/week was associated with reduced odds for osteoporosis; and performing 150-1800 MET-min/week of PA was associated with reduced odds for osteoarthritis after adjust the results by several confounders. CONCLUSIONS: The benefits of PA in sarcopenia, osteoporosis, and osteoarthritis prevention are evident among Americans aged ≥50 years.