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Background: Genetic risk scores (GRSs) have partially improved the understanding of the etiology of moderate hypertriglyceridemia (HTG), which until recently was mainly assessed by secondary predisposing causes. The main objective of this study was to assess whether this variability is due to the interaction between clinical variables and GRS. Methods: We analyzed 276 patients with suspected polygenic HTG. An unweighted GRS was developed with the following variants: c.724C > G (ZPR1 gene), c.56C > G (APOA5 gene), c.1337T > C (GCKR gene), g.19986711A > G (LPL gene), c.107 + 1647T > C (BAZ1B gene) and g.125478730A > T (TRIB gene). Interactions between the GRS and clinical variables (body mass index (BMI), diabetes mellitus, diet, physical activity, alcohol consumption, age and gender) were evaluated. Results: The GRS was associated with triglyceride (TG) concentrations. There was a significant interaction between BMI and GRS, with the intensity of the relationship between the number of alleles and the TG concentration being greater in individuals with a higher BMI. Conclusions: GRS is associated with plasma TG concentrations and is markedly influenced by BMI. This finding could improve the stratification of patients with a high genetic risk for HTG who could benefit from more intensive healthcare interventions.

Background Sarcopenia is a progressive age‐related skeletal muscle disorder associated with increased likelihood of adverse outcomes. Muscle wasting is often accompanied by an increase in body fat, leading to ‘sarcopenic obesity’. The aim of the present study was to analyse the association of lifestyle variables such as diet, dietary components, physical activity (PA), body composition, and inflammatory markers, with the risk of sarcopenic obesity. Methods A cross‐sectional analysis based on baseline data from the PREDIMED‐Plus study was performed. A total of 1535 participants (48% women) with overweight/obesity (body mass index: 32.5 ± 3.3 kg/m2; age: 65.2 ± 4.9 years old) and metabolic syndrome were categorized according to sex‐specific tertiles (T) of the sarcopenic index (SI) as assessed by dual‐energy X‐ray absorptiometry scanning. Anthropometrical measurements, biochemical markers, dietary intake, and PA information were collected. Linear regression analyses were carried out to evaluate the association between variables. Results Subjects in the first SI tertile were older, less physically active, showed higher frequency of abdominal obesity and diabetes, and consumed higher saturated fat and less vitamin C than subjects from the other two tertiles (all P < 0.05). Multiple adjusted linear regression models evidenced significant positive associations across tertiles of SI with adherence to the Mediterranean dietary score (P‐trend < 0.05), PA (P‐trend < 0.0001), and the 30 s chair stand test (P‐trend < 0.0001), whereas significant negative associations were found with an inadequate vitamin C consumption (P‐trend < 0.05), visceral fat and leucocyte count (all P‐trend < 0.0001), and some white cell subtypes (neutrophils and monocytes), neutrophil‐to‐lymphocyte ratio, and platelet count (all P‐trend < 0.05). When models were additionally adjusted by potential mediators (inflammatory markers, diabetes, and waist circumference), no relevant changes were observed, only dietary variables lost significance. Conclusions Diet and PA are important regulatory mediators of systemic inflammation, which is directly involved in the sarcopenic process. A healthy dietary pattern combined with exercise is a promising strategy to limit age‐related sarcopenia.

ObjectiveSLE is associated with increased cardiovascular risk (CVR). High serum concentrations of triglyceride-rich lipoproteins and apolipoprotein B-rich particles constitute the characteristic dyslipidaemia of SLE.MethodsA cross-sectional study was conducted to study the relationship between genetic variants involved in polygenic hypertriglyceridaemia, subclinical atherosclerosis and lipoprotein abnormalities. 73 women with SLE and 73 control women age-matched with the case group were recruited (age range 30–75 years). Serum analysis, subclinical atherosclerosis screening studies for the detection of plaque, and genetic analysis of the APOE, ZPR1, APOA5 and GCKR genes were performed.ResultsTriglyceride concentrations and the prevalence of hypertension, dyslipidaemia and carotid atherosclerosis were higher in women with SLE than in the control group. Multivariate logistic regression showed that CC homozygosity for the GCKR rs1260326 gene (OR=0.111, 95% CI 0.015 to 0.804, p=0.030) and an increase of 1 mmol/L in triglyceride concentrations were associated with a greater risk of carotid plaque in women with SLE (OR=7.576, 95% CI 2.415 to 23.767, p=0.001).ConclusionsGCKR CC homozygosity (rs1260326) and serum triglyceride concentrations are independently associated with subclinical carotid atherosclerosis in women with SLE. Subclinical carotid atherosclerosis is also more prevalent in these women compared with the control group. The study of GCKR rs1260326 gene variants may contribute to more precise assessment of CVR and modulation of the intensity of lipid-lowering treatment in patients with SLE.

Background: Visceral adipose tissue (VAT) has a hazardous influence on systemic inflammation, insulin resistance and an adverse metabolic profile, which increases the risk of developing non-alcoholic fatty liver disease (NAFLD) and chronic complications of diabetes. In our study we aimed to evaluate the association of VAT and the triglyceride glucose (TyG) as a proxy of insulin resistance surrogated with metabolic and liver risk factors among subjects diagnosed with metabolic syndrome (MetS). Methods: A cross-sectional study was performed including 326 participants with MetS (55–75 years) from the PREDIMED-Plus study. Liver-status markers, VAT and TyG were assessed. Participants were stratified by tertiles according to VAT (n = 254) and TyG (n = 326). A receiver operating characteristic curve was used to analyse the efficiency of TyG for VAT. Results: Subjects with greater visceral fat depots showed worse lipid profile, higher homeostatic model assessment for insulin resistance (HOMA-IR), TyG, alanine transaminase (ALT), fibroblast growth factor-21 (FGF-21), fatty liver index (FLI) and hepatic steatosis index (HSI) compared with participants in the first tertile. The multi-adjusted linear-regression analyses indicated that individuals in the third tertile of TyG (>9.1−10.7) had a positive association with HOMA-IR [β = 3.07 (95% confidence interval (CI) 2.28−3.86; p trend < 0.001)], ALT [β = 7.43 (95% CI 2.23−12.63; p trend = 0.005)], gamma glutamyl transferase (GGT) [β = 14.12 (95% CI 3.64−24.61; p trend = 0.008)], FGF-21 [β = 190.69 (95% CI 93.13−288.25; p trend < 0.001)], FLI [β = 18.65 (95% CI 14.97−22.23; p trend < 0.001)] and HSI [β = 3.46 (95% CI, 2.23−4.68; p trend < 0.001)] versus participants from the first tertile. Interestingly, the TyG showed the largest area under the receiver operating curve (AUC) for women (AUC = 0.713; 95% CI 0.62−0.79) compared with men (AUC = 0.570; 95% CI 0.48−0.66). Conclusions: A disrupted VAT enlargement and impairment of TyG are strongly associated with liver status and cardiometabolic risk factors linked with NAFLD in individuals diagnosed with MetS. Moreover, the TyG could be used as a suitable and reliable marker estimator of VAT.

Physical exercise performed regularly is known to improve health and to reduce the risk of age-related diseases. Furthermore, there is some evidence of cognitive improvement in physically active middle-aged and older adults. We hypothesized that long-term physically active middle-aged men may have developed brain resilience that can be detected with the analysis of peripheral blood markers. We aimed to analyze the activation of pathways potentially modulated by physical activity in a cohort of healthy amateur rugby players ( = 24) and control subjects with low physical activity ( = 25) aged 45-65 years. We had previously reported neuropsychological improvement in immediate memory responses in the player group compared to the controls. Here, we tested the expression of selected genes of longevity, inflammation, redox homeostasis, and trophic signaling in whole blood mRNA. Analyses were also performed on blood samples of young (aged 15-25 years) control subjects with low physical activity ( = 21). Physical activity and other lifestyle factors were thoroughly recorded with standardized questionnaires. Interestingly, middle-aged control subjects showed lower levels of expression of SIRT1, SIRT3, CAT, and SOD1 than the young controls, although rugby players maintained the expression levels of these genes at a young-like level. Middle-aged players showed lower levels of IL1B than the non-physically active groups. However, there was a tendency towards a decrease in trophic and transduction factors in middle-aged groups as compared to the young controls. A statistical study of Spearman's correlations supported a positive effect of sporting activity on memory and executive functions, and on peripheral gene expression of SIRT1, SIRT3 and downstream genes, in the middle-aged rugby players. Our results indicate that the SIRT1-SIRT3 axis, and associated neuroprotective signaling, may contribute to the anti-aging resilience of the brain mediated by physical exercise.

Purpose We aimed to evaluate associations between compliance with recommendations for total water intake (TWI) and total water intake from fluids (TWIF), and some socio-demographic and lifestyle factors of a senior Mediterranean population at high cardiovascular risk. Methods Cross-sectional analysis with data of 1902 participants from the PREDIMED-Plus study. A validated 32-item Spanish fluid-intake questionnaire was used to assess beverage consumption and water intake. Multivariable logistic regression models were used to assess the odds ratio (OR) and the 95% confidence interval (CI) for complying with European Food Safety Agency recommendations for TWI and TWIF according to various socio-demographic and lifestyle factors, and for the joint associations of Mediterranean diet (MedDiet) adherence and moderate–vigorous physical activity (MVPA). Results The mean total volume of fluid intake in the population studied was 1934 ± 617 mL/day. Water was the most frequently consumed beverage. Significant differences between sex were only observed in alcoholic and hot beverage consumption. Compliance with TWIF was associated with being women (OR 3.02; 2.40, 3.80), high adherence to MedDiet (OR 1.07; 1.02, 1.12), and participants who were more engaged in physical activity (PA) (OR 1.07; 1.02, 1.13). Age was inversely associated (OR 0.96; 0.94, 0.98). Similar results for TWI recommendations compliance were observed in relation to being women (OR 5.34; 3.85, 7.42), adherence to MedDiet (OR 1.16; 1.02, 1.31) and PA (OR 1.07; 1.00, 1.15). The joint association of PA and MedDiet, showed that participants with higher adherence to MedDiet and meeting WHO recommendations for MVPA complied better with the TWI recommendations (OR 1.66; 1.19, 2.32). Conclusions High compliance with recommendations for TWI was associated with being a woman, and a healthy lifestyle characterized by high adherence to the MedDiet and PA.

The main objective of this study was to determine plasma levels of PS and to study SNVs rs41360247, rs4245791, rs4148217, and rs11887534 of ABCG8 and the r657152 SNV at the ABO blood group locus in a sample of a population treated at our hospital, and to determine whether these SNVs are related to plasma PS concentrations. The secondary objective was to establish the variables associated with plasma PS concentrations in adults. Participants completed a dietary habit questionnaire and a blood sample was collected to obtain the following variables: campesterol, sitosterol, sitostanol, lanosterol, stigmasterol, biochemical parameters, and the SNVs. In addition, biometric and demographic variables were also recorded. In the generalized linear model, cholesterol and age were positively associated with total PS levels, while BMI was negatively related. For rs4245791, homozygous T allele individuals showed a significantly lower campesterol concentration compared with C homozygotes, and the GG alleles of rs657152 had the lowest levels of campesterol compared with the other alleles of the SNV. Conclusions: The screening of certain SNVs could help prevent the increase in plasma PS and maybe PNALD in some patients. However, further studies on the determinants of plasma phytosterol concentrations are needed.

Background: Lipid metabolism disorders, especially hypertriglyceridemia (HTG), are risk factors for non-alcoholic fatty liver disease (NAFLD). However, the association between genetic factors related to HTG and the risk of NAFLD has been scarcely studied. Methods: A total of 185 subjects with moderate HTG were prospectively included. We investigated the association between genetic factors’ (five allelic variants with polygenic hypertriglyceridemia) clinical and biochemical biomarkers with NAFLD severity. The five allelic variants’ related clinical and biochemical data of HTG were studied in all the subjects. NAFLD was assessed by abdominal ultrasound and patients were divided into two groups, one with no or mild NAFLD and another with moderate/severe NAFLD. Results: Patients with moderate/severe NAFLD had higher weight and waist values and a higher prevalence of insulin resistance than patients with no or mild NAFLD. Moderate/severe NAFLD was independently associated with APOA5 rs3134406 and ZPR1 rs964184 variants, and also showed a significant inverse relationship with lipoprotein(a) [Lp(a)] concentrations. Conclusions: APOA5 rs3135506 and ZPR1 rs964184 variants and lipoprotein(a) are associated with moderate/severe NAFLD. This association was independent of body weight, insulin resistance, and other factors related to NAFLD.

Metabolic syndrome (MetS) is associated with alterations of lipoprotein structure and function that can be characterized with advanced lipoprotein testing (ADLT). The effect of the Mediterranean diet (MedDiet) and weight loss on the lipoprotein subclass profile has been scarcely studied. Within the PREDIMED-Plus randomized controlled trial, a sub-study conducted at Bellvitge Hospital recruiting center evaluated the effects of a weight loss program based on an energy-reduced MedDiet (er-MedDiet) and physical activity (PA) promotion (intervention group) compared with energy-unrestricted MedDiet recommendations (control group) on ADLT-assessed lipoprotein subclasses. 202 patients with MetS (n = 107, intervention; n = 95, control) were included. Lipid profiles were determined, and ADLT was performed at baseline, 6, and 12 months. Linear mixed models were used to assess the effects of intervention on lipoprotein profiles. Compared to the control diet, at 12 months, the er-MedDiet+PA resulted in a significant additional 4.2 kg of body weight loss, a decrease in body mass index by 1.4 kg/m2, reduction in waist circumference by 2.2 cm, decreased triglycerides, LDL-cholesterol and non-HDL-cholesterol, and increased HDL-cholesterol. In er-MedDiet+PA participants, ADLT revealed a decrease in small dense-LDL-cholesterol (sd-LDL-C), intermediate-density lipoproteins, VLDL-triglyceride, and HDL-Triglyceride, and an increase in large LDL and large VLDL particles. In conclusion, compared to an ad libitum MedDiet (control group), er-MedDiet+PA decreased plasma triglycerides and the triglyceride content in HDL and VLDL particles, decreased sd-LDL-C, and increased large LDL particles, indicating beneficial changes against cardiovascular disease.

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver morbidity. This condition often is accompanied by obesity, diabetes, and metabolic syndrome (MetS). The aim of this study was to evaluate the connection between lifestyle factors and NAFLD in individuals with MetS. A cross-sectional study with 328 participants (55–75 y of age) diagnosed with MetS participating in the PREDIMED-Plus trial was conducted. NAFLD status was evaluated using the non-invasive hepatic steatosis index (HSI). Sociodemographic, clinical, and dietary data were collected. Adherence to the Mediterranean diet (mainly assessed by the consumption of olive oil, nuts, legumes, whole grain foods, fish, vegetables, fruits, and red wine) and physical activity were assessed using validated questionnaires. Linear regression analyses revealed that HSI values tended to be lower with increasing physical activity tertiles (T2, β = –1.47; 95% confidence interval [CI], –2.73 to –0.20; T3, β = –1.93; 95% CI, –3.22 to –0.65 versus T1, Ptrend = 0.001) and adherence to the Mediterranean diet was inversely associated with HSI values: (moderate adherence β = –0.70; 95% CI, –1.92 to 0.53; high adherence β = –1.57; 95% CI, –3.01 to –0.13 versus lower, Ptrend = 0.041). Higher tertiles of legume consumption were inversely associated with the highest tertile of HSI (T2, relative risk ratio [RRR], 0.45; 95% CI, 0.22–0.92; P = 0.028; T3, RRR, 0.48; 95% CI, 0.24–0.97; P = 0.041 versus T1). Physical activity, adherence to the Mediterranean diet, and consumption of legumes were inversely associated with a non-invasive marker of NAFLD in individuals with MetS. This data can be useful in implementing precision strategies aimed at the prevention, monitoring, and management of NAFLD. •Sedentary lifestyle and lower adherence to the Mediterranean diet is associated with risk for non-alcoholic fatty liver disease in older individuals diagnosed with metabolic syndrome.•Higher legume intake is related to an improvement in liver status.•Recommendations of healthy lifestyles for the prevention and management of non-alcoholic fatty liver disease in patients at high cardiovascular risk are warranted.