Association between serum copper levels and risk of cardiovascular disease: A nested case-control study in the PREDIMED trial.

BACKGROUND AND AIM: Certain trace elements have been associated with increased cardiovascular risk. The aim of this study was to evaluate the association between serum copper (S-Cu) levels and the risk of a first event of cardiovascular disease (CVD) in a population of older adults with high cardiovascular risk. METHODS AND RESULTS: We conducted a case-control study nested within the PREDIMED trial. During a median follow-up of 4.8 years, a total of 207 incident cases diagnosed with CVD were matched for sex, age, and intervention group with 436 controls. Personal interviews, reviews of medical records, and validated questionnaires were used to assess known CVD risk factors. Biological serum samples were collected annually. Inductively coupled plasma mass spectrometry analysis was used to determine S-Cu levels. Adjusted odds ratios were calculated using multivariate conditional logistic regression models. All participants had S-Cu levels within the reference values, 750 µg/L to 1450 µg/L. Among men, but not among women, the mean S-Cu concentration was higher in cases 1014.1 µg/L than in controls 959.3 µg/L; (p = 0.004). In men, the multivariable-adjusted odds ratio for CVD was 2.36 (95% CI 1.07-5.20 for the comparison of the highest vs. the lowest quartile; p for trend = 0.02), in women, it was 0.43 (95% CI 0.11-1.70; p for trend = 0.165). CONCLUSION: In older Spanish men with high cardiovascular risk, a significant association was observed between high S-Cu levels, but still within the reference values, and an increased risk of a first event of CVD. Our findings suggest a sex difference in CVD risk and S-Cu levels. To confirm this relationship and to analyze the differences observed between men and women, further studies are needed.

Multiple approaches to associations of physical activity and adherence to the Mediterranean diet with all-cause mortality in older adults: the PREvención con DIeta MEDiterránea study.

PURPOSE: Although evidence indicates that both physical activity and adherence to the Mediterranean diet (MedDiet) reduce the risk of all-cause mortality, a little is known about optimal intensities of physical activity and their combined effect with MedDiet in older adults. We assessed the separate and combined associations of leisure-time physical activity (LTPA) and MedDiet adherence with all-cause mortality. METHODS: We prospectively studied 7356 older adults (67 ± 6.2 years) at high vascular risk from the PREvención con DIeta MEDiterránea study. At baseline and yearly thereafter, adherence to the MedDiet and LTPA were measured using validated questionnaires. RESULTS: After 6.8 years of follow-up, we documented 498 deaths. Adherence to the MedDiet and total, light, and moderate-to-vigorous LTPA were inversely associated with all-cause mortality (p < 0.01 for all) in multiple adjusted Cox regression models. The adjusted hazard of all-cause mortality was 73% lower (hazard ratio 0.27, 95% confidence interval 0.19-0.38, p < 0.001) for the combined category of highest adherence to the MedDiet (3rd tertile) and highest total LTPA (3rd tertile) compared to lowest adherence to the MedDiet (1st tertile) and lowest total LTPA (1st tertile). Reductions in mortality risk did not meaningfully differ between total, light intensity, and moderate-to-vigorous LTPA. CONCLUSIONS: We found that higher levels of LTPA, regardless of intensity (total, light and moderate-to-vigorous), and greater adherence to the MedDiet were associated separately and jointly with lower all-cause mortality. The finding that light LTPA was inversely associated with mortality is relevant because this level of intensity is a feasible option for older adults.

Chromium Exposure and Risk of Cardiovascular Disease in High Cardiovascular Risk Subjects　- Nested Case-Control Study in the Prevention With Mediterranean Diet (PREDIMED) Study.

BACKGROUND: Epidemiological data on chromium (Cr) exposure and the risk of cardiovascular disease (CVD) are still limited. Toenail Cr level (TCL) provides a time-integrated measure reflecting long-term Cr exposure. We measured TCL to assess the hypothesis that long-term Cr exposure was inversely associated with incident CVD in a population at high risk for CVD.Methods and Results:The associations between TCL and CVD were evaluated in a case-control study nested within the "PREvención con DIeta MEDiterránea" (PREDIMED) trial. We randomly selected 147 of the 288 patients diagnosed with CVD during follow-up and matched them on age and sex to 271 controls. Instrumental neutron activation analysis was used to assess TCL. In-person interviews, medical record reviews, and validated questionnaires were used to assess covariates. The fully adjusted OR for the highest vs. lowest quartile of toenail Cr was 0.54 (95% CI: 0.26-1.14; Ptrend=0.189) for the nested case-control study. On stratification for diabetes mellitus (DM), OR was 1.37 (95% CI: 0.54-3.46; Ptrend=0.364) for the DM group, and 0.25 (95% CI: 0.08-0.80; Ptrend=0.030) for the non-DM group (P for interaction=0.078). CONCLUSIONS: The present findings, although not statistically significant, are consistent with previously reported inverse associations between TCL and CVD. These results, especially for non-DM patients, increase the limited epidemiological knowledge about the possible protective role of Cr against CVD. (Trial registration: www.controlled-trials.com; ISRCTN35739639.).

Frequent Consumption of Sugar- and Artificially Sweetened Beverages and Natural and Bottled Fruit Juices Is Associated with an Increased Risk of Metabolic Syndrome in a Mediterranean Population at High Cardiovascular Disease Risk.

BACKGROUND: The relation between the consumption of sweetened beverages and metabolic syndrome (MetS) is controversial. OBJECTIVE: This analysis evaluated the associations between intakes of sugar-sweetened beverages (SSBs), artificially sweetened beverages, and natural and bottled fruit juices and the incidence of MetS in elderly individuals at high risk of cardiovascular disease (CVD) and without MetS at baseline. METHODS: We prospectively examined 1868 participants free of MetS at baseline from the PREDIMED (PREvención con DIeta MEDiterránea) study. MetS was defined by using the updated harmonized criteria of the International Diabetes Federation, the American Heart Association, and National Heart, Lung, and Blood Institute. Energy and nutrient intakes were evaluated at baseline and then yearly by using a validated 137-item food-frequency questionnaire. Multivariable-adjusted HRs for MetS and its components were estimated from mean intakes during follow-up. We compared the 2 highest consumption categories (1-5 and >5 servings/wk) with the lowest category (<1 serving/wk). RESULTS: A total of 930 incident cases of MetS were documented during a median follow-up of 3.24 y. When we compared consumption of >5 servings/wk with consumption of <1 serving/wk, multivariable HRs (95% CIs) for MetS incidence were 1.43 (1.00, 2.15), 1.74 (1.26, 2.41), 1.30 (1.00, 1.69), and 1.14 (1.04, 1.65) for SSBs, artificially sweetened beverages, natural fruit juices, and bottled fruit juices, respectively. CONCLUSIONS: The occasional consumption of SSBs and artificially sweetened beverages (1-5 servings/wk) was not associated with the incidence of MetS in middle-aged and elderly individuals at high risk of CVD. The consumption of >5 servings/wk of all of the types of beverages analyzed was associated with an increased risk of MetS and some of its components. However, for SSBs and bottled fruit juices these associations must be interpreted with caution because of the low frequency of consumption in this population. This trial was registered at clinicaltrials.gov as ISRCTN35739639.

[Psychosocial stress environment and health workers in public health: Differences between primary and hospital care]. / Entorno psicosocial y estrés en trabajadores sanitarios de la sanidad pública: diferencias entre atención primaria y hospitalaria.

OBJECTIVE: To describe the psychosocial environment of health professionals in public health in primary and hospital care, and compare it with that of the general Spanish working population, as well as to evaluate the effect of psychosocial risk factors on symptoms related to perceived stress. DESIGN: Cross-sectional study with stratified random sampling. SETTING: Health care workers in the province of Granada, distributed in 5 hospitals and 4 health districts. PARTICIPANTS: A total of 738 employees (medical and nursing staff) of the Andalusian Health Service (SAS) were invited to take part. MAIN MEASUREMENTS: CopSoQ/Istas21 questionnaire developed for the multidimensional analysis of the psychosocial work environment. Stress symptoms were measured with the Stress Profile questionnaire. RESULTS: The response rate was 67.5%. Compared with the Spanish workforce, our sample showed high cognitive, emotional, and sensory psychological demands, possibilities for development and sense of direction in their work. Primary care physicians were the group with a worse psychosocial work environment. All the groups studied showed high levels of stress symptoms. Multivariate analysis showed that variables associated with high levels of stress symptom were younger and with possibilities for social relations, role conflict, and higher emotional demands, and insecurity at work. CONCLUSIONS: Our findings support that the psychosocial work environment of health workers differs from that of the Spanish working population, being more unfavorable in general practitioners.

Dietary and Smoking Acrylamide and Prostate Cancer Risk: CAPLIFE Study.

Acrylamide is a probable carcinogen. Its main sources are the diet and tobacco. The association between acrylamide intake from the diet and tobacco and prostate cancer (PCa) has not been previously evaluated. We aimed to evaluate the relationship between dietary acrylamide intake and exposure to acrylamide through cigarettes and PCa risk. A population-based case-control (CAPLIFE) study was conducted, including 428 incident PCa cases and 393 controls. Smoking and dietary information, with a validated food frequency questionnaire, was collected. We calculated the amount of acrylamide from both sources, and tertiles (Ts) were created. Multivariable logistic regression and restricted cubic spline models were applied to assess the association between exposure to acrylamide and PCa risk. The median was similar for acrylamide in both dietary and smoking acrylamide among PCa cases and controls. No association was observed between dietary acrylamide intake and overall PCa risk (adjusted ORT3vsT1 = 0.90 (95% CI 0.59, 1.37)). A risk trend was observed for acrylamide exposure from cigarette smoking (p-trend = 0.032), with the highest odds in those subjects with the high exposure to acrylamide through cigarettes (adjusted ORT3vsT1 = 1.67 (95% CI 0.92, 3.04)). The restricted cubic splines suggested a linear relationship. In conclusion, acrylamide from smoking could be positively associated with PCa risk, but no association was observed for dietary acrylamide.

Serum copper levels and risk of major adverse cardiovascular events: a systematic review and meta-analysis.

Background: Despite the fact that several studies have investigated the association between serum copper levels (S-Cu) and the risk of cardiovascular diseases, this relationship remains unclear. The aims of this study were to investigate the association between S-Cu and risk of major adverse cardiovascular events (MACE), including total stroke, ischemic stroke, hemorrhagic stroke, myocardial infarction and cardiovascular mortality, and identify potential sources of results heterogeneity. Methods: We carried out a systematic review and meta-analysis. The selection criteria were: (1) Observational studies (cohort studies, case-control studies and hybrid studies); (2) Studies containing quantitative data about the relationship between S-Cu and risk of MACE; (3) Estimating association measures; and (4) Studies written in English, French or Spanish. Overall pooled Odds ratio (pOR) and 95% confidence intervals (95% CI) of MACE for the highest vs. lowest S-Cu category were calculated using random-effects models. Results: Sixteen studies with a total of 41,322 participants were included in the meta-analysis: 10 prospective cohort studies, 5 nested case-control studies and 1 case-control study. Comparing highest vs. lowest category, high S-Cu levels were associated with total stroke (pOR: 1.49, 95% CI 1.22-1.82; I2 = 0%, p = 0.54), myocardial infarction (pOR: 1.31, 95% CI 1.17-1.46; I2 = 0.0%, p = 0.92) and cardiovascular mortality (pOR: 1.60, 95% CI 1.39-1.86; I2 = 0.0%, p = 0.54). Subgroup analysis showed that studies with a hybrid design had higher risks for cardiovascular mortality (pOR: 3.42, 95% CI 1.98-5.92) and ischemic stroke (pOR: 1.54, 95% CI 1.30-1.83). Conclusion: High S-Cu levels were associated with an increased risk of total stroke, myocardial infarction and cardiovascular mortality. Hybrid studies seems to modify the strength of the association between S-Cu and the risk of cardiovascular mortality and ischemic stroke. Systematic review registration: [https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022370782], identifier [CRD42022370782].

Mediterranean diet and risk of breast cancer: An umbrella review.

BACKGROUND: The Mediterranean Diet (MedDiet) is a healthy dietary pattern which has been related to a lower risk of certain chronic diseases, such as some cancers. However, its role in breast cancer development remains unclear. This umbrella review aims to summarize the highest available evidence on MedDiet and breast cancer risk. METHODS: Pubmed, Web of Science, and Scopus electronic platforms were searched for relevant systematic reviews and meta-analyses. The selection criteria included systematic reviews with or without meta-analysis including women aged 18 years or older which evaluated the adherence to a MedDiet as the exposure and incidence of breast cancer as the outcome variable. Overlapping and quality of the reviews using AMSTAR-2 tool were independently assessed by two authors. RESULTS: Five systematic reviews and six systematic reviews with meta-analysis were included. Overall, 4 systematic reviews - two with and two without meta-analysis - were rated as of high quality. An inverse association was found in 5 of the 9 reviews which evaluated the role of MedDiet on the risk of total breast cancer. The meta-analyses showed moderate-high heterogeneity. The risk reduction seemed to be more consistent among postmenopausal women. No association was found for MedDiet among premenopausal women. CONCLUSIONS: The results of this umbrella review suggest that adherence to a MedDiet pattern had a protective effect on the risk of breast cancer, especially for postmenopausal breast cancer. The stratification of breast cancer cases and conducting high-quality reviews are aspects needed to overcome the current results' heterogeneity and to improve knowledge in this field.

Comparative effects of glucagon-like peptide-1 receptors agonists, 4-dipeptidyl peptidase inhibitors, and metformin on metabolic syndrome.

AIMS: To assess the comparative effects of glucagon-like peptide-1 receptor agonists (GLP-1RA), 4-dipeptidyl peptidase inhibitors (DPP-4I), and metformin treatment during one year on metabolic syndrome (MetS) components and severity in MetS patients. METHODS: Prospective study (n = 6165 adults) within the frame of PREDIMED-Plus trial. The major end-point was changes on MetS components and severity after one- year treatment of GLP-1RA, DPP-4I, and metformin. Anthropometric measurements (weight, height and waist circumference), body mass index (BM), and blood pressure were registered. Blood samples were collected after overnight fasting. Plasma glucose, glycosylated hemoglobin (HbA1c), plasma triglycerides and cholesterol were measured. Dietary intakes as well as physical activity were assessed through validated questionnaires. RESULTS: MetS parameters improved through time. The treated groups improved glycaemia compared with untreated (glycaemia ∆ untreated: -1.7 mg/dL(± 13.5); ∆ metformin: - 2.5(± 23.9) mg/dL; ∆ DPP-4I: - 4.5(± 42.6); mg/dL ∆ GLP-1RA: - 4.3(± 50.9) mg/dL; and HbA1c: ∆ untreated: 0.0(± 0.3) %; ∆ metformin: - 0.1(± 0.7) %; ∆ DPP-4I: - 0.1(± 1.0) %; ∆ GLP-1RA: - 0.2(± 1.2) %. Participants decreased BMI and waist circumference. GLP-1RA and DPP-4I participants registered the lowest decrease in BMI (∆ untreated: -0.8(± 1.6) kg/m2; ∆ metformin: - 0.8(± 1.5) kg/m2; ∆ DPP-4I: - 0.6(± 1.3) kg/m2; ∆ GLP-1RA: - 0.5(± 1.2) kg/m2. and their waist circumference (∆ untreated: -2.8(± 5.2) cm; ∆ metformin: - 2.6(± 15.2) cm; ∆ DPP-4I: - 2.1(± 4.8) cm; ∆ GLP-1RA: - 2.4(± 4.1) cm. CONCLUSION: In patients with MetS and healthy lifestyle intervention, those treated with GLP-1RA and DPP-4I obtained better glycemic profile. Anthropometric improvements were modest.

Dietary Iron, Anemia Markers, Cognition, and Quality of Life in Older Community-Dwelling Subjects at High Cardiovascular Risk.

Anemia causes hypo-oxygenation in the brain, which could lead to cognitive disorders. We examined dietary iron intake as well as anemia markers (i.e., hemoglobin, hematocrit, mean corpuscular volume) and diabetes coexistence in relation to neuropsychological function and quality of life. In this study, 6117 community-dwelling adults aged 55-75 years (men) and 60-75 years (women) with overweight/obesity and metabolic syndrome were involved. We performed the Mini-Mental State Examination (MMSE), the Trail Making Test parts A and B (TMT-A/B), Semantic Verbal Fluency of animals (VFT-a), Phonological Verbal Fluency of letter P (VFT-p), Digit Span Test (DST), the Clock Drawing Test (CDT), and the Short Form-36 Health Survey (SF36-HRQL test). Dietary iron intake did not influence neuropsychological function or quality of life. However, anemia and lower levels of anemia markers were associated with worse scores in all neurophysiological and SF36-HRQL tests overall, but were especially clear in the MMSE, TMT-B (cognitive flexibility), and the physical component of the SF36-HRQL test. The relationships between anemia and diminished performance in the TMT-A/B and VFT tasks were notably pronounced and statistically significant solely among participants with diabetes. In brief, anemia and reduced levels of anemia markers were linked to inferior cognitive function, worse scores in different domains of executive function, as well as a poorer physical, but not mental, component of quality of life. It was also suggested that the coexistence of diabetes in anemic patients may exacerbate this negative impact on cognition. Nevertheless, dietary iron intake showed no correlation with any of the outcomes. To make conclusive recommendations for clinical practice, our findings need to be thoroughly tested through methodologically rigorous studies that minimize the risk of reverse causality.

Serum Selenium and Incident Cardiovascular Disease in the PREvención con DIeta MEDiterránea (PREDIMED) Trial: Nested Case-Control Study.

Background: Selenium is an essential trace mineral with potential interest for cardiovascular disease (CVD) prevention owing to its antioxidant properties. Epidemiological data on selenium status and CVD remain inconsistent. The objective of this study was to ascertain whether low serum selenium (SSe) concentrations are related to an increased risk of a first CVD event in a population at high cardiovascular risk. Methods: We undertook a case-control study nested within the "PREvención con DIeta MEDiterránea" (PREDIMED) trial. A total of 207 participants diagnosed with CVD (myocardial infarction, stroke, or cardiovascular death) during the follow-up period (2003−2010) were matched by sex, age, and intervention group to 436 controls by incidence density sampling. Median time between serum sample collection and subsequent CVD event occurrence was 0.94 years. SSe levels were determined using inductively coupled plasma mass spectrometry analysis. Covariates were assessed through validated questionnaires, in-person interviews, and medical record reviews. Conditional logistic regression was used to calculate multivariable-adjusted odds ratios (ORs). Results: Among women, the mean SSe concentration was lower in cases than in controls (98.5 µg/L vs. 103.8 µg/L; p = 0.016). In controls, SSe levels were directly associated with percentage of total energy intake from proteins and fish intake (p for linear trend < 0.001 and 0.049, respectively), whereas SSe concentrations were inversely associated with age, body mass index, and percentage of total energy intake from carbohydrates (p for linear trend < 0.001, 0.008 and 0.016 respectively). In the total group, we observed an inverse dose−response gradient between SSe levels and risk of CVD in the fully-adjusted model (highest vs. lowest quartile: OR = 0.47, 95% CI: 0.27−0.81; ptrend = 0.003). Conclusions: Among elderly individuals at high cardiovascular risk, high SSe concentrations within population reference values are associated with lower first CVD incidence.

Associations Between the Modified Food Standard Agency Nutrient Profiling System Dietary Index and Cardiovascular Risk Factors in an Elderly Population.

Background: Helping consumers to improve the nutritional quality of their diet is a key public health action to prevent cardiovascular diseases (CVDs). The modified version of the Food Standard Agency Nutrient Profiling System Dietary Index (FSAm-NPS DI) underpinning the Nutri-Score front-of-pack label has been used in public health strategies to address the deleterious consequences of poor diets. This study aimed to assess the association between the FSAm-NPS DI and some CVD risk factors including body mass index (BMI), waist circumference, plasma glucose levels, triglyceride levels, high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol, and diastolic and systolic blood pressure. Materials and Methods: Dietary intake was assessed at baseline and after 1 year of follow-up using a 143-item validated semi-quantitative food-frequency questionnaire. Dietary indices based on FSAm-NPS applied at an individual level were computed to characterize the diet quality of 5,921 participants aged 55-75 years with overweight/obesity and metabolic syndrome from the PREDIMED-plus cohort. Associations between the FSAm-NPS DI and CVD risk factors were assessed using linear regression models. Results: Compared to participants with a higher nutritional quality of diet (measured by a lower FSAm-NPS DI at baseline or a decrease in FSAm-NPS DI after 1 year), those participants with a lower nutritional quality of diet (higher FSAm-NPS DI or an increase in score) showed a significant increase in the levels of plasma glucose, triglycerides, diastolic blood pressure, BMI, and waist circumference (ß coefficient [95% confidence interval]; P for trend) (1.67 [0.43, 2.90]; <0.001; 6.27 [2.46, 10.09]; <0.001; 0.56 [0.08, 1.05]; 0.001; 0.51 [0.41, 0.60]; <0.001; 1.19 [0.89, 1.50]; <0.001, respectively). No significant associations in relation to changes in HDL and LDL-cholesterol nor with systolic blood pressure were shown. Conclusion: This prospective cohort study suggests that the consumption of food items with a higher FSAm-NPS DI is associated with increased levels of several major risk factors for CVD including adiposity, fasting plasma glucose, triglycerides, and diastolic blood pressure. However, results must be cautiously interpreted because no significant prospective associations were identified for critical CVD risk factors, such as HDL and LDL-cholesterol, and systolic blood pressure.

Morbid liver manifestations are intrinsically bound to metabolic syndrome and nutrient intake based on a machine-learning cluster analysis.

Metabolic syndrome (MetS) is one of the most important medical problems around the world. Identification of patient´s singular characteristic could help to reduce the clinical impact and facilitate individualized management. This study aimed to categorize MetS patients using phenotypical and clinical variables habitually collected during health check-ups of individuals considered to have high cardiovascular risk. The selected markers to categorize MetS participants included anthropometric variables as well as clinical data, biochemical parameters and prescribed pharmacological treatment. An exploratory factor analysis was carried out with a subsequent hierarchical cluster analysis using the z-scores from factor analysis. The first step identified three different factors. The first was determined by hypercholesterolemia and associated treatments, the second factor exhibited glycemic disorders and accompanying treatments and the third factor was characterized by hepatic enzymes. Subsequently four clusters of patients were identified, where cluster 1 was characterized by glucose disorders and treatments, cluster 2 presented mild MetS, cluster 3 presented exacerbated levels of hepatic enzymes and cluster 4 highlighted cholesterol and its associated treatments Interestingly, the liver status related cluster was characterized by higher protein consumption and cluster 4 with low polyunsaturated fatty acid intake. This research emphasized the potential clinical relevance of hepatic impairments in addition to MetS traditional characterization for precision and personalized management of MetS patients.

Mediterranean Diet and Physical Activity Decrease the Initiation of Cardiovascular Drug Use in High Cardiovascular Risk Individuals: A Cohort Study.

Our aim was to assess whether long-term adherence to a Mediterranean diet (MedDiet) and leisure-time physical activity (LTPA) were associated with a lower initiation of cardiovascular drug use. We studied the association between cumulative average of MedDiet adherence and LTPA and the risk of cardiovascular drug initiation in older adults at high cardiovascular risk (PREvención con DIeta MEDiterránea trial participants) non-medicated at baseline: glucose-lowering drugs (n = 4437), antihypertensives (n = 2145), statins (n = 3977), fibrates (n = 6391), antiplatelets (n = 5760), vitamin K antagonists (n = 6877), antianginal drugs (n = 6837), and cardiac glycosides (n = 6954). One-point increases in MedDiet adherence were linearly associated with a decreased initiation of glucose-lowering (HR: 0.76 [0.71-0.80]), antihypertensive (HR: 0.79 [0.75-0.82]), statin (HR: 0.82 [0.78-0.85]), fibrate (HR: 0.78 [0.68-0.89]), antiplatelet (HR: 0.79 [0.75-0.83]), vitamin K antagonist (HR: 0.83 [0.74; 0.93]), antianginal (HR: 0.84 [0.74-0.96]), and cardiac glycoside therapy (HR: 0.69 [0.56-0.84]). LTPA was non-linearly related to a delayed initiation of glucose-lowering, antihypertensive, statin, fibrate, antiplatelet, antianginal, and cardiac glycoside therapy (minimum risk: 180-360 metabolic equivalents of task-min/day). Both combined were synergistically associated with a decreased onset of glucose-lowering drugs (p-interaction = 0.04), antihypertensive drugs (p-interaction < 0.001), vitamin K antagonists (p-interaction = 0.04), and cardiac glycosides (p-interaction = 0.01). Summarizing, sustained adherence to a MedDiet and LTPA were associated with lower risk of initiating cardiovascular-related medications.

Glycolysis/gluconeogenesis- and tricarboxylic acid cycle-related metabolites, Mediterranean diet, and type 2 diabetes.

BACKGROUND: Glycolysis/gluconeogenesis and tricarboxylic acid (TCA) cycle metabolites have been associated with type 2 diabetes (T2D). However, the associations of these metabolites with T2D incidence and the potential effect of dietary interventions remain unclear. OBJECTIVES: We aimed to evaluate the association of baseline and 1-y changes in glycolysis/gluconeogenesis and TCA cycle metabolites with insulin resistance and T2D incidence, and the potential modifying effect of Mediterranean diet (MedDiet) interventions. METHODS: We included 251 incident T2D cases and 638 noncases in a nested case-cohort study within the PREDIMED Study during median follow-up of 3.8 y. Participants were allocated to MedDiet + extra-virgin olive oil, MedDiet + nuts, or control diet. Plasma metabolites were measured using a targeted approach by LC-tandem MS. We tested the associations of baseline and 1-y changes in glycolysis/gluconeogenesis and TCA cycle metabolites with subsequent T2D risk using weighted Cox regression models and adjusting for potential confounders. We designed a weighted score combining all these metabolites and applying the leave-one-out cross-validation approach. RESULTS: Baseline circulating concentrations of hexose monophosphate, pyruvate, lactate, alanine, glycerol-3 phosphate, and isocitrate were significantly associated with higher T2D risk (17-44% higher risk for each 1-SD increment). The weighted score including all metabolites was associated with a 30% (95% CI: 1.12, 1.51) higher relative risk of T2D for each 1-SD increment. Baseline lactate and alanine were associated with baseline and 1-y changes of homeostasis model assessment of insulin resistance. One-year increases in most metabolites and in the weighted score were associated with higher relative risk of T2D after 1 y of follow-up. Lower risks were observed in the MedDiet groups than in the control group although no significant interactions were found after adjusting for multiple comparisons. CONCLUSIONS: We identified a panel of glycolysis/gluconeogenesis-related metabolites that was significantly associated with T2D risk in a Mediterranean population at high cardiovascular disease risk. A MedDiet could counteract the detrimental effects of these metabolites.This trial was registered at controlled-trials.com as ISRCTN35739639.

Dietary inflammatory index and all-cause mortality in large cohorts: The SUN and PREDIMED studies.

BACKGROUND: Inflammation is known to be related to the leading causes of death including cardiovascular disease, several types of cancer, obesity, type 2 diabetes, depression-suicide and other chronic diseases. In the context of whole dietary patterns, the Dietary Inflammatory Index (DII®) was developed to appraise the inflammatory potential of the diet. OBJECTIVE: We prospectively assessed the association between DII scores and all-cause mortality in two large Spanish cohorts and valuated the consistency of findings across these two cohorts and results published based on other cohorts. DESIGN: We assessed 18,566 participants in the "Seguimiento Universidad de Navarra" (SUN) cohort followed-up during 188,891 person-years and 6790 participants in the "PREvencion con DIeta MEDiterránea" (PREDIMED) randomized trial representing 30,233 person-years of follow-up. DII scores were calculated in both cohorts from validated FFQs. Higher DII scores corresponded to more proinflammatory diets. A total of 230 and 302 deaths occurred in SUN and PREDIMED, respectively. In a random-effect meta-analysis we included 12 prospective studies (SUN, PREDIMED and 10 additional studies) that assessed the association between DII scores and all-cause mortality. RESULTS: After adjusting for a wide array of potential confounders, the comparison between extreme quartiles of the DII showed a positive and significant association with all-cause mortality in both the SUN (hazard ratio [HR] = 1.85; 95% CI: 1.15, 2.98; P-trend = 0.004) and the PREDIMED cohort (HR = 1.42; 95% CI: 1.00, 2.02; P-trend = 0.009). In the meta-analysis of 12 cohorts, the DII was significantly associated with an increase of 23% in all-cause mortality (95% CI: 16%-32%, for the highest vs lowest category of DII). CONCLUSION: Our results provide strong and consistent support for the hypothesis that a pro-inflammatory diet is associated with increased all-cause mortality. The SUN cohort and PREDIMED trial were registered at clinicaltrials.gov as NCT02669602 and at isrctn.com as ISRCTN35739639, respectively.

Risk of peripheral artery disease according to a healthy lifestyle score: The PREDIMED study.

BACKGROUND AND AIMS: The PREDIMED (PREvención con DIeta MEDiterránea) is a multicentre trial analyzed as a prospective cohort study. A total of 7122 participants (aged 55-80 years) at high risk of cardiovascular disease in the PREDIMED trial were recruited in 11 centres in Spain. The prevalence of subjects with type 2 diabetes was 50%. Our objective was to determine the contribution of lifestyle factors to the development of peripheral artery disease (PAD). METHODS: Incident clinical PAD in relation to a healthy lifestyle 5-point score defined as adherence to a Mediterranean diet (MedDiet), moderate alcohol intake, regular physical activity, normal weight (BMI<25) and non-smoking was measured. RESULTS: Eighty-seven incident PAD cases were diagnosed during a median follow-up of 4.8 years. Compared with participants with 0 or 1 healthy lifestyle factor, the multivariable hazard ratio for PAD was 0.65 (95% confidence interval (CI) 0.37 to 1.14) for 2 factors, and 0.40 (0.22-0.72) for 3 or more. Moderate alcohol consumption, non-smoking, physical activity and following a MedDiet were significantly inversely associated with PAD whereas no association was found for normal weight (BMI<25 kg/m2). PAD risk monotonically decreased with an increasing number of lifestyle factors, and the greatest reduction was found for a score combining moderate alcohol consumption, MedDiet and physical activity or non-smoking. The multivariable-adjusted population attributable risk percent for the combination of these 4 factors was 80.5% (95% CI: 21.3%-95.1%). CONCLUSIONS: Our results demonstrate that a simple healthy lifestyle score is associated with a substantially reduced risk of PAD in a high cardiovascular risk population with a high prevalence (50%) of subjects with type 2 diabetes.

Psychiatric Status across Body Mass Index in a Mediterranean Spanish Population.

BACKGROUND: Mental and body weight disorders are among the major global health challenges, and their comorbidity may play an important role in treatment and prevention of both pathologies. A growing number of studies have examined the relationship between psychiatric status and body weight, but our knowledge is still limited. OBJECTIVE: The present study aims to investigate the cross-sectional relationships of psychiatric status and body mass index (BMI) in Málaga, a Mediterranean city in the South of Spain. MATERIALS AND METHODS: A total of 563 participants were recruited from those who came to his primary care physician, using a systematic random sampling, non-proportional stratified by BMI categories. Structured clinical interviews were used to assess current Axes-I and II mental disorders according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR). BMI was calculated as weight (Kg) divided by square of height in meters (m2). Logistic regression was used to investigate the association between BMI and the presence of any mental disorder. BMI was introduced in the models using restricted cubic splines. RESULTS: We found that high BMI values were directly associated with mood and adjustment disorders, and low BMI values were directly associated with avoidant and dependent personality disorders (PDs). We observed an inverse relationship between low BMI values and cluster A PDs. There were not significant relationships between anxiety or substance-related disorders and BMI. CONCLUSION: Psychiatric status and BMI are related in a Mediterranean Spanish population. A multidisciplinary approach to both pathologies becomes increasingly more necessary.

Weight status and psychological distress in a Mediterranean Spanish population: a symmetric U-shaped relationship.

Psychological disorders in people with extreme weight (low weight or obesity) should be taken into consideration by health professionals in order to practice an effective treatment to these patients. This study evaluates the association between body mass index (BMI) and psychological distress in 563 inhabitants of Málaga (South of Spain). Participants were classified in four categories of BMI: Underweight (BMI <18.5 Kg/m2), Normal weight (BMI 18.5-24.99 Kg/m2), Overweight (BMI 25.0-29.99 Kg/m2) and Obesity (BMI >30 Kg/m2). Psychological distress was measured with the Spanish version of the Derogatis' Symptoms Checklist Revised (SCL-90-R). We observed a symmetric U-shaped relationship between weight status and psychological distress in all SCL-90-R dimensions (p for quadratic trend <0.001) for both men and women. Participants with extreme weight showed the worst psychological status, and participants with normal weight exhibited the best. We found no statistically significant differences between underweight and obese participants in 9 of the 10 SCL-90-R dimensions analyzed among men, and in 8 of the 10 dimensions among women. Underweight and obese participants showed no gender differences in psychological distress levels. Psychological treatment of Mediterranean people with extreme weight, should consider underweight and obese patients at the same level of psychological distress.

Predicting the onset of anxiety syndromes at 12 months in primary care attendees. The predictA-Spain study.

BACKGROUND: There are no risk algorithms for the onset of anxiety syndromes at 12 months in primary care. We aimed to develop and validate internally a risk algorithm to predict the onset of anxiety syndromes at 12 months. METHODS: A prospective cohort study with evaluations at baseline, 6 and 12 months. We measured 39 known risk factors and used multilevel logistic regression and inverse probability weighting to build the risk algorithm. Our main outcome was generalized anxiety, panic and other non-specific anxiety syndromes as measured by the Primary Care Evaluation of Mental Disorders, Patient Health Questionnaire (PRIME-MD-PHQ). We recruited 3,564 adult primary care attendees without anxiety syndromes from 174 family physicians and 32 health centers in 6 Spanish provinces. RESULTS: The cumulative 12-month incidence of anxiety syndromes was 12.2%. The predictA-Spain risk algorithm included the following predictors of anxiety syndromes: province; sex (female); younger age; taking medicines for anxiety, depression or stress; worse physical and mental quality of life (SF-12); dissatisfaction with paid and unpaid work; perception of financial strain; and the interactions sex*age, sex*perception of financial strain, and age*dissatisfaction with paid work. The C-index was 0.80 (95% confidence interval=0.78-0.83) and the Hedges' g=1.17 (95% confidence interval=1.04-1.29). The Copas shrinkage factor was 0.98 and calibration plots showed an accurate goodness of fit. CONCLUSIONS: The predictA-Spain risk algorithm is valid to predict anxiety syndromes at 12 months. Although external validation is required, the predictA-Spain is available for use as a predictive tool in the prevention of anxiety syndromes in primary care.