Change to a healthy diet in people over 70 years old: the PREDIMED experience.

PURPOSE: It is difficult to change dietary habits and maintain them in the long run, particularly in elderly people. We aimed to assess whether adherence to the Mediterranean diet (MedDiet) and cardiovascular risk factor were similar in the middle-aged and oldest participants in the PREDIMED study. METHODS: We analyzed participants belonging to the first and fourth quartiles of age (Q1 and Q4, respectively) to compare between-group differences in adherence to the nutritional intervention and cardiovascular risk factor (CRF) control during a 3-year follow-up. All participants underwent yearly clinical, nutritional, and laboratory assessments during the following. RESULTS: A total of 2278 patients were included (1091 and 1187 in Q1 and Q4, respectively). At baseline, mean ages were 59.6 ± 2.1 years in Q1 and 74.2 ± 2.6 years in Q4. In Q4, there were more women, greater prevalence of hypertension and diabetes, and lower obesity and smoking rates than the younger cohort (P ≤ 0.001, all). Adherence to the MedDiet was similar in Q1 and Q4 at baseline (mean 8.7 of 14 points for both) and improved significantly (P < 0.01) and to a similar extent (mean 10.2 and 10.0 points, respectively) during follow-up. Systolic blood pressure, low density-lipoprotein cholesterol, and body weight were similarly reduced at 3 years in Q1 and Q4 participants. CONCLUSION: The youngest and oldest participants showed improved dietary habits and CRFs to a similar extent after 3 years' intervention. Therefore, it is never too late to improve dietary habits and ameliorate CRF in high-risk individuals, even those of advanced age. REGISTRATION: The trial is registered in the London-based Current Controlled Trials Registry (ISRCTN number 35739639).

Factors associated with successful dietary changes in an energy-reduced Mediterranean diet intervention: a longitudinal analysis in the PREDIMED-Plus trial.

PURPOSE: Long-term nutrition trials may fail to respond to their original hypotheses if participants do not comply with the intended dietary intervention. We aimed to identify baseline factors associated with successful dietary changes towards an energy-reduced Mediterranean diet (MedDiet) in the PREDIMED-Plus randomized trial. METHODS: Longitudinal analysis of 2985 participants (Spanish overweight/obese older adults with metabolic syndrome) randomized to the active intervention arm of the PREDIMED-Plus trial. Dietary changes were assessed with a 17-item energy-reduced MedDiet questionnaire after 6 and 12 months of follow-up. Successful compliance was defined as dietary changes from baseline of ≥ 5 points for participants with baseline scores < 13 points or any increase if baseline score was ≥ 13 points. We conducted crude and adjusted multivariable logistic regression models to identify baseline factors related to compliance. RESULTS: Consistent factors independently associated with successful dietary change at both 6 and 12 months were high baseline perceived self-efficacy in modifying diet (OR6-month: 1.51, 95% CI 1.25-1.83; OR12-month: 1.66, 95% CI 1.37-2.01), higher baseline fiber intake (OR6-month: 1.62, 95% CI 1.07-2.46; OR12-month: 1.62, 95% CI 1.07-2.45), having > 3 chronic conditions (OR6-month: 0.65, 95% CI 0.53-0.79; OR12-month: 0.76, 95% CI 0.62-0.93), and suffering depression (OR6-month: 0.80, 95% CI 0.64-0.99; OR12-month: 0.71, 95% CI 0.57-0.88). CONCLUSION: Our results suggested that recruitment of individuals with high perceived self-efficacy to dietary change, and those who initially follow diets relatively richer in fiber may lead to greater changes in nutritional recommendations. Participants with multiple chronic conditions, specifically depression, should receive specific tailored interventions. TRIAL REGISTRATION: ISRCTN registry 89898870, 24th July 2014 retrospectively registered http://www.isrctn.com/ISRCTN89898870 .

Effect of an Intensive Weight-Loss Lifestyle Intervention on Kidney Function: A Randomized Controlled Trial.

INTRODUCTION: Large randomized trials testing the effect of a multifactorial weight-loss lifestyle intervention including Mediterranean diet (MedDiet) on renal function are lacking. Here, we evaluated the 1-year efficacy of an intensive weight-loss intervention with an energy-reduced MedDiet (erMedDiet) plus increased physical activity (PA) on renal function. METHODS: Randomized controlled "PREvención con DIeta MEDiterránea-Plus" (PREDIMED-Plus) trial is conducted in 23 Spanish centers comprising 208 primary care clinics. Overweight/obese (n = 6,719) adults aged 55-75 years with metabolic syndrome were randomly assigned (1:1) to an intensive weight-loss lifestyle intervention with an erMedDiet, PA promotion, and behavioral support (intervention) or usual-care advice to adhere to an energy-unrestricted MedDiet (control) between September 2013 and December 2016. The primary outcome was 1-year change in estimated glomerular filtration rate (eGFR). Secondary outcomes were changes in urine albumin-to-creatinine ratio (UACR), incidence of moderately/severely impaired eGFR (<60 mL/min/1.73 m2) and micro- to macroalbuminuria (UACR ≥30 mg/g), and reversion of moderately (45 to <60 mL/min/1.73 m2) to mildly impaired GFR (60 to <90 mL/min/1.73 m2) or micro- to macroalbuminuria. RESULTS: After 1 year, eGFR declined by 0.66 and 1.25 mL/min/1.73 m2 in the intervention and control groups, respectively (mean difference, 0.58 mL/min/1.73 m2; 95% CI: 0.15-1.02). There were no between-group differences in mean UACR or micro- to macroalbuminuria changes. Moderately/severely impaired eGFR incidence and reversion of moderately to mildly impaired GFR were 40% lower (HR 0.60; 0.44-0.82) and 92% higher (HR 1.92; 1.35-2.73), respectively, in the intervention group. CONCLUSIONS: The PREDIMED-Plus lifestyle intervention approach may preserve renal function and delay CKD progression in overweight/obese adults.

Effect of changes in adherence to Mediterranean diet on nutrient density after 1-year of follow-up: results from the PREDIMED-Plus Study.

BACKGROUND: The prevalence of overweight/obesity and related manifestations such as metabolic syndrome (MetS) is increasing worldwide. High energy density diets, usually with low nutrient density, are among the main causes. Some high-quality dietary patterns like the Mediterranean diet (MedDiet) have been linked to the prevention and better control of MetS. However, it is needed to show that nutritional interventions promoting the MedDiet are able to improve nutrient intake. OBJECTIVE: To assess the effect of improving MedDiet adherence on nutrient density after 1 year of follow-up at the PREDIMED-Plus trial. METHODS: We assessed 5777 men (55-75 years) and women (60-75 years) with overweight or obesity and MetS at baseline from the PREDIMED-Plus trial. Dietary changes and MedDiet adherence were evaluated at baseline and after 1 year. The primary outcome was the change in nutrient density (measured as nutrient intake per 1000 kcal). Multivariable-adjusted linear regression models were fitted to analyse longitudinal changes in adherence to the MedDiet and concurrent changes in nutrient density. RESULTS: During 1-year follow-up, participants showed improvements in nutrient density for all micronutrients assessed. The density of carbohydrates (- 9.0%), saturated fatty acids (- 10.4%) and total energy intake (- 6.3%) decreased. These changes were more pronounced in the subset of participants with higher improvements in MedDiet adherence. CONCLUSIONS: The PREDIMED-Plus dietary intervention, based on MedDiet recommendations for older adults, maybe a feasible strategy to improve nutrient density in Spanish population at high risk of cardiovascular disease with overweight or obesity.

Nutrition and Cardiovascular Health.

Cardiovascular disease (CVD) is the leading cause of death in Western countries, representing almost 30% of all deaths worldwide. Evidence shows the effectiveness of healthy dietary patterns and lifestyles for the prevention of CVD. Furthermore, the rising incidence of CVD over the last 25 years has become a public health priority, especially the prevention of CVD (or cardiovascular events) through lifestyle interventions. Current scientific evidence shows that Western dietary patterns compared to healthier dietary patterns, such as the 'Mediterranean diet' (MeDiet), leads to an excessive production of proinflammatory cytokines associated with a reduced synthesis of anti-inflammatory cytokines. In fact, dietary intervention allows better combination of multiple foods and nutrients. Therefore, a healthy dietary pattern shows a greater magnitude of beneficial effects than the potential effects of a single nutrient supplementation. This review aims to identify potential targets (food patterns, single foods, or individual nutrients) for preventing CVD and quantifies the magnitude of the beneficial effects observed. On the other hand, we analyze the possible mechanisms implicated in this cardioprotective effect.

Anti-Inflammatory Effects of the Mediterranean Diet in the Early and Late Stages of Atheroma Plaque Development.

Objective. To evaluate the long-term effects of a Mediterranean diet (MeDiet) intervention on the plasma concentrations of inflammatory and plaque stability-related molecules in elderly people at high risk for cardiovascular disease. Design and Setting. 66 participants from primary care centers affiliated with the Hospital Clinic of Barcelona were randomized into 3 groups: MeDiet plus extra virgin olive oil (EVOO) or nuts and a low-fat diet (LFD). At baseline and at 3 and 5 years, we evaluated the changes in the plasma concentrations of 24 inflammatory biomarkers related to the different stages of the atherosclerotic process by Luminex®. Results. At 3 and 5 years, both MeDiet groups showed a significant reduction of IL-6, IL-8, MCP-1, and MIP-1ß (P < 0.05; all) compared to LFD. IL-1ß, IL-5, IL-7, IL-12p70, IL-18, TNF-α, IFN-γ, GCSF, GMCSF, and ENA78 (P < 0.05; all) only decreased in the MeDiet+EVOO group and E-selectin and sVCAM-1 (P < 0.05; both) in the MeDiet+nuts group. Conclusions. Long-term adherence to MeDiet decreases the plasma concentrations of inflammatory biomarkers related to different steps of atheroma plaque development in elderly persons at high cardiovascular risk.

Long-Term Immunomodulatory Effects of a Mediterranean Diet in Adults at High Risk of Cardiovascular Disease in the PREvención con DIeta MEDiterránea (PREDIMED) Randomized Controlled Trial.

BACKGROUND: The Mediterranean diet (MedDiet) has demonstrated short-term anti-inflammatory effects, but little is known about its long-term immunomodulatory properties. OBJECTIVE: Our goal was to assess the long-term effects of the MedDiet on inflammatory markers related to atherogenesis in adults at high risk of cardiovascular disease (CVD) compared with the effects of a low-fat diet (LFD). METHODS: We randomly assigned 165 high-risk participants (one-half men; mean age: 66 y) without overt CVD to 1 of 3 diets: a MedDiet supplemented with extra-virgin olive oil, a MedDiet supplemented with nuts, or an LFD. Follow-up data were collected at 3 and 5 y. Repeated-measures ANOVA, adjusted for potential confounding variables, was used to evaluate changes in diet adherence, CVD risk factors, and inflammatory variables. RESULTS: The 2 MedDiet groups achieved a high degree of adherence to the intervention, and the LFD group had reduced energy intake from fat by 13% by 5 y. Compared with baseline, at 3 and 5 y, both MedDiet groups had significant reductions of ≥16% in plasma concentrations of high-sensitivity C-reactive protein, interleukin-6, tumor necrosis factor α, and monocyte chemoattractant protein 1 (P ≤ 0.04), whereas there were no significant changes in the LFD group. The reductions in CD49d and CD40 expressions in T lymphocytes and monocytes at 3 y were ≥16% greater in both MedDiet groups than were the changes in the LFD group (P < 0.001) at 3 y. Compared with baseline, at 3 y, the MedDiet groups had increased HDL-cholesterol (≥8%) and decreased blood pressure (>4%) and total cholesterol, LDL-cholesterol, and triglyceride (≥8%) concentrations. At 5 y, concentrations of glucose (13%) and glycated hemoglobin (8%) had increased with the LFD. CONCLUSIONS: The MedDiet participants had lower cellular and plasma concentrations of inflammatory markers related to atherosclerosis at 3 and 5 y. This anti-inflammatory role of the MedDiet could explain in part the long-term cardioprotective effect of the MedDiet against CVD. This trial was registered at controlled-trials.com as ISRCTN35739639.

Dealcoholized red wine decreases systolic and diastolic blood pressure and increases plasma nitric oxide: short communication.

RATIONALE: Experimental studies have shown a potential blood pressure (BP) lowering effect of red wine polyphenols, whereas the effects of ethanol and polyphenols on BP in humans are not yet clear. OBJECTIVE: The aim of the present work was to evaluate the effects of red wine fractions (alcoholic and nonalcoholic) on BP and plasma nitric oxide (NO) in subjects at high cardiovascular risk. METHODS AND RESULTS: Sixty-seven men at high cardiovascular risk were studied. After a 2-week run-in period, subjects were randomized into 3 treatment periods in a crossover clinical trial, with a common background diet plus red wine (30g alcohol/day), the equivalent amount of dealcoholized red wine, or gin (30g alcohol/day), lasting 4 weeks each intervention. At baseline and after each intervention, anthropometrical parameters, BP and plasma NO were measured. Systolic and diastolic BP decreased significantly after the dealcoholized red wine intervention and these changes correlated with increases in plasma NO. CONCLUSIONS: Dealcoholized red wine decreases systolic and diastolic BP. Our results point out through an NO-mediated mechanism. The daily consumption of dealcoholized red wine could be useful for the prevention of low to moderate hypertension. Trial registered at controlled-trials.com: ISRCTN88720134.

Validation of a pregnancy-adapted Mediterranean Diet Adherence Screener (preg-MEDAS): a validation study nested in the Improving Mothers for a better PrenAtal Care Trial BarCeloNa (IMPACT BCN) trial.

BACKGROUND: Non-time-consuming and easy-to-administer dietary assessment tools specific for pregnancy are needed. OBJECTIVES: The aim of this validation study nested in the IMPACT BCN (Improving Mothers for a better PrenAtal Care Trial BarCeloNa) trial is to determine the concurrent validity of the 17-item pregnancy-adapted Mediterranean diet score (preg-MEDAS) and to analyze whether changes in the preg-MEDAS score were associated with maternal favorable dietary and cardiometabolic changes after 3 mo of intervention in pregnant women. METHODS: Dietary data was collected in 812 participants using the preg-MEDAS and a 151-item validated food frequency questionnaire (FFQ) at baseline (19-23 wk gestation) and final visit (31-34 wk gestation). Concurrent preg-MEDAS validity was evaluated by Pearson and intraclass correlation coefficients, κ statistic, and Bland-Altman methods. RESULTS: The preg-MEDAS had a good correlation with the FFQ (r = 0.76 and intraclass correlation coefficient 0.75). The agreement of each of the preg-MEDAS items ranged from 40.9% to 93.8% with a substantial agreement mean concordance (κ = 0.61). A 2-point increase in preg-MEDAS was associated with a decrease in maternal mean and systolic blood pressure (ß: -0.51 mmHg; 95% confidence interval [CI]: -0.97, -0.04 mmHg and -0.87 mmHg; 95% CI: -1.48, -0.26 mmHg, respectively). CONCLUSIONS: The preg-MEDAS displays good validity for assessing adherence to the Mediterranean diet, allowing detection of dietary changes over time. In addition, changes observed in preg-MEDAS are significantly associated with a decrease in maternal blood pressure. Therefore, we propose preg-MEDAS as a rapid and simple dietary assessment tool during pregnancy. This trial was registered at clinicaltrials.gov as NCT03166332.

Unlocking the power of polyphenols: A promising biomarker of improved metabolic health and anti-inflammatory diet in adolescents.

BACKGROUND: Metabolic syndrome (MetS) in adolescence is a risk factor for future cardiovascular disease. The chronic inflammation associated with MetS can be attenuated by the anti-inflammatory effect of polyphenols. We aimed to evaluate total urinary polyphenols as a biomarker of anti-inflammatory diets and their effect on MetS in adolescents. METHODS: In this retrospective analysis of a longitudinal cohort study, the relationship between total polyphenol excretion (TPE) in urine, the inflammatory potential of the diet measured through the Children's Dietary Inflammatory Index (C-DII), and the presence of metabolic syndrome was evaluated. The study population consisted of adolescents enrolled in the SI! Program for Secondary Schools trial, who had completed all the study forms and provided urine samples at baseline and at the two-year follow-up. Multivariate linear regression and multinominal logistic regression models were generated to evaluate the relationship of changes in TPE with changes in the C-DII score and changes in MetS status, respectively. An analysis of the ROC curve was performed to assess the potential of TPE as a biomarker of an anti-inflammatory diet. RESULTS: This study included 662 adolescents, 51.2% were males, and 48.8% were females, with a mean age of 12 (0.38) years at baseline. The relationship between changes in TPE and changes in the C-DII score was stratified by sex with a p-value <0.001 for the interaction. TPE and C-DII were inversely associated in males (-0.13 mg GAE/g creatinine [-0.26; -0.01] per 1-SD increase, p-value = 0.037). In addition, an increase in changes in TPE levels were associated with a reversal in MetS status in all adolescents (1.30 [1.27; 1.34] per 1-SD increase, p-value<0.001). The ROC curve showed that urinary TPE levels can predict dietary inflammatory potential with an AUC = 0.793 (0.725; 0.863) in males. CONCLUSION: Polyphenols excreted in urine are a potential biomarker of anti-inflammatory diets in males and are associated with a reversal of MetS status in adolescents. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, Identifier: NCT03504059, https://clinicaltrials.gov/study/NCT03504059.

Diet quality and nutrient density in pregnant women according to adherence to Mediterranean diet.

Background and aims: The dietary pattern followed during pregnancy, specifically healthy dietary patterns such as the Mediterranean diet, is a key factor in the mother's and the offspring's health. Pregnant women dietary intake is not enough to cover the micronutrient requirements of pregnancy, and higher adherence to the Mediterranean diet may improve dietary quality and nutritional density. The aim of the present study was to describe the dietary nutrient intake and diet quality during pregnancy and to evaluate whether a high adherence to Mediterranean diet was associated with a more adequate intake of micronutrients. Methods: This was a cross-sectional study with 1,356 pregnant women selected during the routine second trimester ultrasound scan (19-23 weeks' gestation). Energy and nutrient intake were calculated using a validated 151-item semi-quantitative food frequency questionnaire and nutrient density was estimated dividing the absolute nutrient intake by total energy intake. Adherence to the Mediterranean diet was evaluated with a 17-item Mediterranean diet adherence score. The criterion used for risk of inadequate nutrient intake has been set below two thirds (2/3) of the dietary reference intakes. The differences were assessed by multivariate linear regression models adjusted for confounders. Results: A significant proportion of pregnant women had an inadequate intake of macro and micronutrient that was lower in those with high adherence to the Mediterranean diet (≥12 points, n = 122, 19%), including calcium (the Mediterranean diet high adherence 2.5% vs. low adherence 26.7%, p < 0.001), magnesium (0% vs. 7.6%, p = 0.001), iron (24.5% vs. 74.1%, p < 0.001), and vitamin B9 (0% vs. 29.8%, p < 0.001), vitamin C (0% vs. 1.9%, p = 0.033), and vitamin D (61.5% vs. 92.8%, p < 0.001) intake. High adherence to Mediterranean diet was associated with higher intake of protein, monounsaturated fatty acids, fiber, vitamins (B1, B9, C, D), calcium, magnesium, iron, zinc, phosphor, potassium, essential fatty acids, and α-linolenic acid, and with a lower intake of α-linoleic acid and trans fatty acids as compared to low adherence to Mediterranean diet. Conclusion: High adherence to Mediterranean diet was associated with higher diet quality and lower proportion of inadequate micro and macronutrient intake. The Mediterranean diet promotion, particularly among pregnant women, may be a useful and public health strategy to avoid overweight and nutrient deficiencies.

Loss of Visceral Fat is Associated with a Reduction in Inflammatory Status in Patients with Metabolic Syndrome.

SCOPE: Excessive visceral adipose tissue (VAT) is associated with higher secretion of pro-inflammatory molecules, contributing to systemic inflammation and obesity-related metabolic disturbances. METHODS AND RESULTS: This prospective analysis includes 117 overweight/obese adults (55-75 years) from the PREDIMED-Plus study. Fourteen inflammatory markers and adipokines are measured using a Bio-Plex assay with multiplex technology: insulin, glucagon, IL-6, visfatin, ghrelin, GLP-1, TNF-α, MCP-1, PAI-1, resistin, C-peptide, leptin, adipsin, and adiponectin. Participants are categorized into tertiles according to changes in VAT after 1-year of follow-up, determined by dual-energy X-Ray absorptiometry. Participants allocate in tertile 3, which represent an increase of VAT content after 1-year of follow-up compared to tertile 1, show significant differences in insulin (T3 vs T1, fully adjusted model: p = 0.037, p for trend 0.042), PAI-1 (fully adjusted model: p = 0.05, p for trend 0.06), c-peptide (fully adjusted model: p = 0.037, p for trend 0.042), and TNF-α (fully adjusted model p = 0.037, p for trend 0.042). CONCLUSION: The results evidence that a reduction in VAT is associated with clinical improvements in several inflammatory and adiposity markers, mainly in insulin, c-peptide, and PAI-1 levels, and these improvements may contribute to a reduction in cardiometabolic disturbances observe in obesity.

Two-Year Changes in Physical Activity and Concurrent Changes in Cognitive Function in a Cohort of Adults with Metabolic Syndrome.

BACKGROUND: It has been proposed that physical activity (PA) could prevent cognitive decline. OBJECTIVE: To evaluate the association between changes in PA and changes in cognitive function in a cohort of adults with metabolic syndrome. METHODS: Longitudinal observational study including 5,500 adults (mean age 65 years, SD = 5; women = 49.3% ) with metabolic syndrome. Participants underwent physical activity measurements and cognitive evaluation at baseline and at two-years of follow-up. PA was quantified using the Minnesota questionnaire-shortened version. Cognitive function was evaluated using a battery of tests: Mini-Mental Test Examination, Clock Drawing Test, Trail Making Test A and B, Verbal Fluency Test, and Digit Span. The primary outcome was two-year change in cognition, measured through the Global Composite Score (GCS) of all neuropsychological tests. Multivariable-adjusted linear regression models were fitted with baseline PA and their changes as the main exposures and changes in cognitive function as the outcome. RESULTS: No significant association was found between PA levels (or their changes) in the GCS of cognitive function. A greater increase in PA levels was associated with a more favorable two-year change in the Trail Making Test A (Q4 versus Q1: b = - 2.24s, 95% CI -4.36 to -0.12s; p-trend = 0.020). No significant association was found for other neuropsychological test. CONCLUSION: Our results do not support an association between increases in PA and the evolution of the global cognitive function at two-year in an intervention trial which included PA promotion in one of its two randomized arms, but they suggested a possible beneficial effect of PA on attentional function in older adults.

A Comparative Study of the Efficacy of an Intervention with a Nutritional Supplement for Patients with Chronic Kidney Disease: A Randomized Trial.

Chronic kidney disease (CKD) involves heterogeneous diseases that affect the renal structure and function. Malnutrition plays a crucial role during patients with CKD on hemodialysis (HD) treatment and is associated with an increased rate and duration of hospitalizations. The aim of this randomized, parallel, intervention-controlled trial was to assess whether the use of daily supplementation with a new nutritional product developed by the Grand Fontaine Laboratories improves the nutritional status and anthropometric parameters of stage 5 CKD patients, compared with standard renal dietary advice, after three months of follow-up. Dietary intake, anthropometric measurements, physical activity, and blood samples were collected at baseline and after three months of intervention. Significant improvements were observed within the intervention group in body weight (1.5 kg [95% CI: 0.9 to 2.12 kg]) and BMI (0.54 kg/m2 [95% CI: 0.31 to 0.77]; p-value between groups, 0.002 and 0.006, respectively). In the control group, significant decreases were observed in transferrin saturation (-5.04% [95% CI: -8.88 to -1.21]) and alpha-tocopherol levels (-3.31 umol/L [95% CI: -6.30 to -0.32]). We concluded that daily dietary intake of a specific renal nutritional complement in CKD patients with or at risk of malnutrition may prevent deterioration in nutritional parameters.

Increased myostatin activity and decreased myocyte proliferation in chronic alcoholic cardiomyopathy.

BACKGROUND: Apoptosis mediates in alcohol-induced heart damage leading to cardiomyopathy (CMP). Myocyte proliferation may compensate for myocyte loss. Myostatin is upregulated after cardiac damage and by alcohol consumption thereby decreasing myocyte renewal. We assess the potential role of alcohol in inducing myocyte apoptosis as well as in inhibiting myocyte proliferation. METHODS: Heart samples were obtained from organ donors, including 22 high alcohol consumers, 22 with hypertension, 8 with other causes of CMP, and 10 healthy donors. Evaluation included medical record with data on daily, recent and lifetime ethanol consumption, chest X-ray, left ventricular (LV) function assessed by two-dimensional echocardiography, and LV histology and immunohistochemistry. Apoptosis was evaluated by TUNEL, BAX, and BCL-2 assays. Myocyte proliferation was evaluated with Ki-67 assay. Myostatin activity was measured with a specific immunohistochemical assay. CMP was assessed by functional and histological criteria. RESULTS: Alcoholic and hypertensive donors with CMP showed higher apoptotic indices than did their partners without CMP. Myostatin activity was higher in alcoholics than in controls, mainly in those with CMP. The increase in myostatin expression in alcoholic CMP was higher than in other groups. The Ki-67 proliferation index increased in all groups with CMP compared to those without CMP, with alcoholics showing a lower increase in this proliferation response. CONCLUSIONS: Alcohol produces cardiac myocyte loss through apoptosis but also partially inhibits myocyte proliferation through myostatin up-regulation. The final result may suppose an imbalance in myocyte homeostasis, with a net loss in total ventricular myocyte mass and progressive ventricular dysfunction.

Functional status and quality of life 12 months after discharge from a medical ICU in healthy elderly patients: a prospective observational study.

INTRODUCTION: Long-term outcomes of elderly patients after medical ICU care are little known. The aim of the study was to evaluate functional status and quality of life of elderly patients 12 months after discharge from a medical ICU. METHODS: We prospectively studied 112/230 healthy elderly patients (≥ 65 years surviving at least 12 months after ICU discharge) with full functional autonomy without cognitive impairment prior to ICU entry. The main diagnoses at admission using the Acute Physiology and Chronic Health Evaluation III (APACHE III) classification diagnosis and length of ICU stay and ICU scores (APACHE II, Sepsis-related Organ Failure Assessment (SOFA) and OMEGA) at admission and discharge were collected. Comprehensive geriatric assessment included the presence of the main geriatric syndromes and the application of Lawton, Barthel, and Charlson Indexes and Informant Questionnaire on Cognitive Decline to evaluate functionality, comorbidity and cognitive status, respectively. The EuroQol-5D assessed quality of life. Data were collected at baseline, during ICU and ward stay and 3, 6 and 12 months after hospital discharge. Paired or unpaired T-tests compared differences between groups (continuous variables), whereas the chi-square and Fisher exact tests were used for comparing dichotomous variables. For variables significant (P ≤ 0.1) on univariate analysis, a forward multiple regression analysis was performed. RESULTS: Only 48.9% of patients (mean age: 73.4 ± 5.5 years) were alive 12 months after discharge showing a significant decrease in functional autonomy (Lawton and Barthel Indexes) and quality of life (EuroQol-5D) compared to baseline status (P < 0.001, all). Multivariate analysis showed a higher Barthel Index and EQ-5D vas at hospital discharge to be associated factors of full functional recovery (P < 0.01, both). Thus, in patients with a Barthel Index ≥ 60 or EQ-5D vas ≥ 40 at discharge the hazard ratio for full functional recovery was 4.04 (95% CI: 1.58 to 10.33; P = 0.005) and 6.1 (95% CI: 1.9 to 19.9; P < 0.01), respectively. Geriatric syndromes increased after ICU stay and remained significantly increased during follow-up (P < 0.001). CONCLUSIONS: The survival rate of elderly medical patients 12 months after discharge from the ICU is low (49%), although functional status and quality of life remained similar to baseline in most of the survivors. However, there was a two-fold increase in the prevalence of geriatric syndromes.

Evaluation of myocyte proliferation in alcoholic cardiomyopathy: telomerase enzyme activity (TERT) compared with Ki-67 expression.

AIMS: Although the human heart was classically considered a terminal organ, recent studies have reported a myocyte proliferation response versus some aggressions. Excessive ethanol consumption induces development of cardiomyopathy (CMP) through myocyte apoptosis. We evaluated myocyte proliferation response in the heart of chronic alcoholic donors with telomerase activity (telomerase reverse transcriptase (TERT)) compared with Ki-67 nuclear expression. METHODS: Heart samples were prospectively obtained from organ donors on life support. We included donors with (1) high lifetime alcohol consumption (n = 15), (2) longstanding hypertension (n = 14), (3) other causes of CMP (valve, coronary or idiopathic) (n = 8) and (4) previously healthy donors (n = 6). Groups 2 and 3 were subdivided according to the presence of CMP. Evaluation comprised parameters of ethanol consumption, left ventricular function by chest X-ray and 2D echocardiography, and histology and immunohistochemical studies. Myocyte proliferation was evaluated using an assay for Ki-67 expression and measuring telomerase gene activity by real-time PCR. RESULTS: Forty-three donors were included in the study, 35 having CMP. Nuclear Ki-67 activity was low in healthy controls and significantly increased in the other groups, mainly in those with CMP. Alcoholics with CMP had a non-significantly lower proliferation response than the other CMP groups. No proliferation activity was detected with TERT in any case. CONCLUSION: Heart Ki-67 proliferation activity increases in organ donors with CMP, independently of its origin. Alcoholics presented non-significant lower myocyte proliferation capacity compared with the other groups of CMP. TERT activity was not a useful marker of proliferation in this model. Ki-67 is a better procedure to evaluate proliferation than TERT expression in alcohol-induced heart damage.

Deprivation Index and Lifestyle: Baseline Cross-Sectional Analysis of the PREDIMED-Plus Catalonia Study.

This baseline cross-sectional analysis from data acquired in a sub-sample of the PREDIMED-Plus study participants aimed to evaluate the relation between the Composite Socioeconomic Index (CSI) and lifestyle (diet and physical activity). This study involved 1512 participants (759 (52.2%) women) between 55 and 80 years with overweight/obesity and metabolic syndrome assigned to 137 primary healthcare centers in Catalonia, Spain. CSI and lifestyle (diet and physical activity) were assessed. Multiple linear regression or multinomial regression were applied to the data. Cluster analysis was performed to identify dietary patterns. The multiple linear regression model showed that a high deprivation index was related to a higher consumption of refined cereals (11.98 g/d, p-value = 0.001) and potatoes (6.68 g/d, p-value = 0.001), and to a lower consumption of fruits (-17.52 g/d, p-value = 0.036), and coffee and tea (-8.03 g/d, p-value = 0.013). Two a posteriori dietary patterns were identified by cluster analysis and labeled as "healthy" and "unhealthy". In addition, the multinomial regression model showed that a high deprivation index was related to an unhealthy dietary pattern and low physical activity (OR 1.42 [95% CI 1.06-1.89]; p-value < 0.05). In conclusion, a high deprivation index was related to an unhealthy lifestyle (diet and physical activity) in PREDIMED-Plus study participants.

The 3-Year Effect of the Mediterranean Diet Intervention on Inflammatory Biomarkers Related to Cardiovascular Disease.

The intervention with the Mediterranean diet (MD) pattern has evidenced short-term anti-inflammatory effects, but little is known about its long-term anti-inflammatory properties at molecular level. This study aims to investigate the 3-year effect of MD interventions compared to low-fat diet (LFD) on changes on inflammatory biomarkers related to atherosclerosis in a free-living population with a high-risk of cardiovascular disease (CD). Participants (n = 285) in the PREDIMED trial were randomly assigned into three intervention groups: MD with extra-virgin olive oil (EVOO) or MD-Nuts, and a LFD. Fourteen plasma inflammatory biomarkers were determined by Luminex assays. An additional pilot study of gene expression (GE) was determined by RT-PCR in 35 participants. After 3 years, both MDs showed a significant reduction in the plasma levels of IL-1ß, IL-6, IL-8, TNF-α, IFN-γ, hs-CRP, MCP-1, MIP-1ß, RANTES, and ENA78 (p < 0.05; all). The decreased levels of IL-1ß, IL-6, IL-8, and TNF-α after MD significantly differed from those in the LFD (p < 0.05). No significant changes were observed at the gene level after MD interventions, however, the GE of CXCR2 and CXCR3 tended to increase in the control LFD group (p = 0.09). This study supports the implementation of MD as a healthy long-term dietary pattern in the prevention of CD in populations at high cardiovascular risk.