Aims
The aim of this study was to evaluate the effect of the Mediterranean diet (MedDiet) on the incidence of heart failure (HF), a pre‐specified secondary outcome in the PREDIMED (PREvención con ...DIeta MEDiterránea) primary nutrition‐intervention prevention trial.
Methods and results
Participants at high risk of cardiovascular disease were randomly assigned to one of three diets: MedDiet supplemented with extra‐virgin olive oil (EVOO), MedDiet supplemented with nuts, or a low‐fat control diet. Incident HF was ascertained by a Committee for Adjudication of events blinded to group allocation. Among 7403 participants without prevalent HF followed for a median of 4.8 years, we observed 29 new HF cases in the MedDiet with EVOO group, 33 in the MedDiet with nuts group, and 32 in the control group. No significant association with HF incidence was found for the MedDiet with EVOO and MedDiet with nuts, compared with the control group hazard ratio (HR) 0.68; 95% confidence interval (CI) 0.41–1.13, and HR 0.92; 95% CI 0.56–1.49, respectively.
Conclusion
In this sample of adults at high cardiovascular risk, the MedDiet did not result in lower HF incidence. However, this pre‐specified secondary analysis may have been underpowered to provide valid conclusions. Further randomized controlled trials with HF as a primary outcome are needed to better assess the effect of the MedDiet on HF risk.
Trial registration: ISRCTN35739639.
Short dietary assessment tools can be useful to estimate food intake and diet quality in large-scale epidemiological studies with time constraints.
To determine the concurrent validity of the 17-item ...energy-restricted Mediterranean Adherence Screener (er-MEDAS) used in the PREDIMED (PREvención con DIeta MEDiterránea)-Plus trial and to analyse its capacity to detect 1-year changes in diet and cardiometabolic risk factors.
Validation study nested in the PREDIMED-Plus (n = 6760, 55–75 years). Dietary data were collected by the 17-item er-MEDAS and a 143-item validated semiquantitative food frequency questionnaire (FFQ) at baseline and after 1-year intervention. Cardiometabolic risk markers were measured at both time points. A Mediterranean diet (MedDiet) score was derived from both instruments. Concurrent validity was evaluated by Pearson and intra-class correlation coefficients (ICC) and Bland and Altman limits of agreement. Construct validity was evaluated by assessing 1-year changes in FFQ-reported dietary intake and cardiometabolic profile changes in relation to changes in er-MEDAS.
A moderate to good correlation between the MedDiet score calculated by both measurement instruments was found: r = 0.61 and ICC = 0.60 (both p < 0.001). Agreement of each of the er-MEDAS items ranged from 55.4% to 85.0% with a moderate mean concordance (kappa = 0.41). Between baseline and 1-year follow-up, energy intake measured by the FFQ decreased by 242 kcal, while Mediterranean food consumption increased in participants with the highest increase in the er-MEDAS MedDiet score. An increase in the er-MEDAS MedDiet score ratings was associated with a decrease in BMI, waist circumference, triglycerides, fasting glucose, diastolic blood pressure, and triglycerides/HDL-cholesterol ratio (p < 0.001 for all), and with an increase in HDL-cholesterol (p = 0.006).
The er-MEDAS shows a modest to good concurrent validity compared with FFQ data. It shows acceptable construct validity, as a greater er-MEDAS score was associated with more favourable dietary and cardiometabolic profiles over time.
ISRCTN89898870; registration date, 24 July 2014. https://www.isrctn.com/ISRCTN89898870.
Current recommendations for echocardiographic assessment of diastolic function (2016 guidelines of the American Society of Echocardiography (ASE)/European Association of Cardiovascular Imaging ...(EACVI) in patients with metabolic syndrome and overweight/obesity result in a significant number of patients with indeterminate diastolic dysfunction (LVDD). The aim of this article is to study whether the use of the left atrial strain criterion (LALS) reduces the number of indeterminate patients.
229 patients were studied with a complete echocardiographic study that included left ventricular longitudinal strain (LVLS) analysis, LALS and a maximal ergospirometry test with assessment of oxygen uptake (VO2max).
The mean age was 65 ± 5 years, 153 (67%) males, with a mean EF of 60 ± 5%. The mean LVLS was −19.4 ± 2% and the LALS Reservoir was 23.8 ± 7%. There were 140 patients who did not meet LVDD criteria and 82 who did meet the indeterminate LVDD criterion. When the left atrial volume index (LAVI) >34 ml/m2 criterion was replaced in the 2016 ASE/EACVI algorithm by LALS Reservoir ≤20%, the number of indeterminate patients was reduced from 36% to 23% (p < 0.001) at the expense of increasing normal studies (61% and 74%). Adding the LALS Reservoir criterion ≤23% in the 82 patients of the indeterminate group resulted in two groups with a different VO2max (11.6 ± 3 and 18 ± 5 ml/kg/min, p:0.081).
This study confirms the low prevalence of diastolic dysfunction in overweight/obese patients with metabolic syndrome. Adding left atrial strain criterion to the current recommendations significantly reduces the number of indeterminate patients by reclassifying them as normal.
•Diastolic dysfunction is often associated with metabolic syndrome and overweight/obesity.•Guidelines for echocardiographic diagnosis of diastolic dysfunction show a high proportion of indeterminate studies.•It explores the usefulness of longitudinal left atrial strain for echocardiographic assessment of diastolic function.•The use of this parameter reduces the number of indeterminate patients when applying current recommendations.
: Lifestyles influence atrial fibrillation (AF) risk. Determining the effect of lifestyle interventions on blood concentrations of biomarkers of AF-related pathways could help understand AF ...pathophysiology and contribute to AF prevention.
: We studied 532 participants enrolled in the PREDIMED-Plus trial, a Spanish randomized trial conducted in adults (55-75 years) with metabolic syndrome and body mass index between 27-40 kg/m
. Eligible participants were randomized 1:1 to an intensive lifestyle intervention, emphasizing physical activity, weight loss, and adherence to an energy-reduced Mediterranean diet or to a control group. Serum biomarkers carboxy-terminal propeptide of procollagen type I (PICP), high-sensitivity troponin T (hsTnT), high-sensitivity C reactive protein (hsCRP), 3-nitrotyrosine (3-NT), and N-terminal propeptide of B-type natriuretic peptide (NT-proBNP) were measured at baseline, 3 and 5 years after randomization. Mixed models were used to evaluate the effect of intervention on changes in biomarkers through year 5. Mediation analysis was performed to examine the proportion mediated by each component of the intervention.
: At baseline, participants' mean age was 65, 40% were female, and 50% were assigned to the intervention. After five years, mean changes in log-transformed biomarkers were -0.01 (PICP), 0.20 (hsTnT), -0.17 (hsCRP), 0.12 (3-NT), and 0.27 (NT-proBNP). Compared to the control group, participants in the intervention group experienced greater decreases in hsCRP (-14%, 95% confidence interval (CI) -26%, 0%) or smaller increases in 3-NT (-16%, 95% CI -25%, -5%) and NT-proBNP (-12%, 95% CI -23%, 1%). The intervention had minimal impact on hsTnT (-3%, 95% CI -7%, 2%) or PICP concentrations (-2%, 95% CI -9%, 6%). The effect of the intervention on hsCRP was primarily mediated by weight loss (89% at year 5).
: Over five years, a dietary and lifestyle intervention for weight-loss favorably affected concentrations of hsCRP, 3-NT, and NT-proBNP, pointing to specific mechanisms in pathways linking lifestyles and AF.
Nocturnin (NOC) is a unique deadenylase with robust rhythmic expression involved in the regulation of metabolic processes in mammals. Currently, the possible presence of NOC in fish is unknown. This ...report aimed to identify NOC in a fish model, the goldfish ( Carassius auratus), and to study the possible regulation of its expression by feeding. Two partial-length cDNAs of 293 and 223 bp, named nocturnin-a ( noc-a) and nocturnin-b ( noc-b), were identified and found to be highly conserved among vertebrates. Both mRNAs show a similar widespread distribution in central and peripheral tissues, with higher levels detected for noc-a compared with noc-b. The periprandial expression profile revealed that noc-a mRNAs rise sharply after a meal in hypothalamus, intestinal bulb, and liver, whereas almost no changes were observed for noc-b. Food deprivation was found to exert opposite effects on the expression of both NOCs (generally inhibitory for noc-a, and stimulatory for noc-b) in the three mentioned tissues. A single meal after a 48-h food deprivation period reversed (totally or partially) the fasting-induced decreases in noc-a transcripts in all studied tissues and the increases in noc-b expression in the intestinal bulb. Together, this study offers the first report of NOC in fish and shows a high dependence of its expression on feeding and nutritional status. The differential responses to feeding of the two NOCs raise the possibility that they might be underlying different physiological mechanisms (e.g., food intake, lipid mobilization, energy homeostasis) in fish.
Limited longitudinal studies have been conducted to evaluate colorectal cancer (CRC) incidence based on the updated 2018 World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) ...recommendations or other global lifestyle indices, and none in aged populations at high cardiovascular risk. We aimed to assess the association between CRC incidence and adherence to two emerging lifestyles indices (2018 WCRF/AICR score and another low-risk lifestyle (LRL) score comprising smoking status, alcohol consumption, physical activity, diet, and body mass index) in the Spanish PREvencion con DIeta MEDiterranea (PREDIMED) cohort. We studied 7216 elderly men and women at high cardiovascular risk. The 2018 WCRF/AICR and LRL scores were calculated. Multivariable Cox proportional regression models were fitted to estimate the HRs (hazard ratios) and 95% confidence intervals (CIs) for incident CRC events. During a median interquartile range (IQR) follow-up of 6.0 (4.4-7.3) years, 97 CRC events were considered. A significant linear association was observed between each 1-point increment in the WCRF/AICR score (score range from 0 to 7) and CRC risk (HR (95% CI) = 0.79 (0.63-0.99)). Similarly, each 1-point increment in the LRL score (score range from 0 to 5) was associated with a 22% reduction in CRC risk (0.78 (0.64-0.96)). Adhering to emergent lifestyle scores might substantially reduce CRC incidence in elderly individuals. Further longitudinal studies, which take different lifestyle indexes into account, are warranted in the future.
The aim of the present study was to investigate how photocycle and feeding-time cues regulate the daily expression of Per1a, Per2a, Per3, and Cry3 in the goldfish hindgut. For this purpose, we ...studied the daily rhythmicity of these genes in fish maintained under different lighting conditions and under different feeding regimes (scheduled or not). We also studied whether the timing of just one meal is able to reset the hindgut molecular clock. In a first experiment, randomly fed fish were divided into four groups and kept under different light conditions for 30 d: 12 h light and 12 h dark (12L:12D), an inverted photoperiod (12D:12L), constant darkness (24D), and constant light (24L). In a second study, fish maintained under 24L were divided into four groups fed at different time points for 35 d: (1) fish scheduled-fed once a day (at 10:00 h); (2) fish fed with a 12-h shifted schedule (at 22:00 h), (3) fish fed at 10:00 h throughout the experiment, except the last day when fed at 22:00 h; and (4) a randomly fed group of fish. Fish were sacrificed every 6 h throughout a 24-h cycle. In both experiments, gPer1a, gPer2a, gPer3, and gCry3 transcripts were quantified using Real Time-qPCR in the hindgut. Results show the clock genes gPer1a, gPer2a, and gCry3 are synchronized by both zeitgebers, the photocycle and feeding regime, in goldfish hindgut. Moreover, such clock genes anticipate light-on and food delivery, when these cues appear in a cyclic manner. In the absence of both zeitgebers, gCry3 and gPer2a rhythmicity disappeared. In contrast, the gPer1 rhythm was maintained under 24L and random feeding conditions, but not always, suggesting that food when randomly supplied is able to reset the clock depending on other factors, such as the energetic and metabolic conditions of the fish. The expression of gPer2a was not activated during the light phase of the cycle, suggesting the hindgut of goldfish is a non-direct photosensitive organ. In contrast to the other three genes, gPer3 expression in the goldfish hindgut seemed to be dependent on the timing of the last food delivery, even in the presence of a photocycle. This gene was the only one that maintained daily rhythms under both constant lighting conditions (24D and 24L), although with lower amplitude than when a photocycle was present. This indicates that, although the acrophase (peak time) of the gPer3 expression rhythm seems to be driven by feeding time, there is an interaction of both zeitgebers, food and light, to regulate its expression. In conclusion, present data indicate: (1) the hindgut of goldfish can be synchronized in vivo by both the photocycle and feeding time; (2) food is a potent signal that entrains this peripheral oscillator; and (3) both environmental cues seems to target different elements of the molecular clock. (Author correspondence: eisornaa@bio.ucm.es)
Left ventricle diastolic dysfunction (LVDD) is a common finding in high risk individuals, its presence being associated with reduced exercise capacity (EC). We assessed the prevalence of LVDD, ...applying the 2016 guidelines of the American Society of Echocardiography (ASE)/European Association of Cardiovascular Imaging (EACVI), in a population with overweight/obesity and metabolic syndrome and its association with EC.
This was a prospective, cross-sectional study of a cohort of 235 patients (mean age of 65 ± 5 years old and 33% female) without heart disease and an ejection fraction >50% who underwent a complete echocardiographic assessment and cardiopulmonary exercise testing. Individuals meeting three or more criteria of the 2016 ASE/EACVI guidelines are considered to have LVDD, while tests are considered indeterminate in those meeting only two. Overall, 178 (76%) of our patients met one echocardiographic cutoff value for LVDD, 91 (39%) met two and 7 (3%) three or more. Patients meeting three cutoffs values showed a significant reduction in maximal oxygen uptake (16 ± 3 vs. 19.6 ± 5 ml/kg/min, p < .05), unlike those with indeterminate tests. In multiple regression analysis, meeting three cutoffs was associated with number of METS (ß = −2.2, p = .018). In exploratory analysis, using two criteria based on cutoffs different from those proposed in the guidelines, we identified groups with different EC.
The application of 2016 ASE/EACVI guidelines limited the prevalence of LVDD to 3%. This group showed a clear reduction of the EC. New echocardiographic cutoff values proposed in this study allow us to establish subgroups with different levels of EC.
It is well established in mammals that the gastrointestinal tract (GIT) senses the luminal presence of nutrients and responds to such information by releasing signaling molecules that ultimately ...regulate feeding. However, gut nutrient sensing mechanisms are poorly known in fish. This research characterized fatty acid (FA) sensing mechanisms in the GIT of a fish species with great interest in aquaculture: the rainbow trout (
). Main results showed that: (i) the trout GIT has mRNAs encoding numerous key FA transporters characterized in mammals (FA transporter CD36 -FAT/CD36-, FA transport protein 4 -FATP4-, and monocarboxylate transporter isoform-1 -MCT-1-) and receptors (several free FA receptor -Ffar- isoforms, and G protein-coupled receptors 84 and 119 -Gpr84 and Gpr119-), and (ii) intragastrically-administered FAs differing in their length and degree of unsaturation (i.e., medium-chain (octanoate), long-chain (oleate), long-chain polyunsaturated (α-linolenate), and short-chain (butyrate) FAs) exert a differential modulation of the gastrointestinal abundance of mRNAs encoding the identified transporters and receptors and intracellular signaling elements, as well as gastrointestinal appetite-regulatory hormone mRNAs and proteins. Together, results from this study offer the first set of evidence supporting the existence of FA sensing mechanisms n the fish GIT. Additionally, we detected several differences in FA sensing mechanisms of rainbow trout vs. mammals, which may suggest evolutionary divergence between fish and mammals.
It has been suggested that melatonin is synthesized in nonphotosensitive organs of vertebrates in addition to the well-known sites of the pineal gland and retina. However, very few studies have ...demonstrated the gene expression of melatonin-synthesizing enzymes in extrapineal and extraretinal locations. This study focuses on the circadian expression of the two key enzymes of the melatoninergic pathway, arylalkylamine N-acetyltransferase (AANAT) and hydroxyindole-O-methyltransferase (HIOMT), in central and peripheral locations of a teleost fish, the goldfish (Carassius auratus). First, the full-length cDNA sequences corresponding to the goldfish AANAT-2 (gAanat-2) and HIOMT-2 (gHiomt-2) were cloned, showing high similarity with other teleost sequences. Two forms of AANAT exist in teleosts. Here, for the first time, two isoforms of HIOMT are deduced from phylogenetic analysis. Moreover, both HIOMT and AANAT were detected in several peripheral locations, including liver and gut, the present results being the first to find HIOMT in nonphotosensitive structures of a fish species. Second, quantitative real-time polymerase chain reaction (PCR) studies were performed to investigate regulation of gAanat-2 in pineal and peripheral locations of goldfish maintained under different lighting conditions. The current results show circadian rhythms in Aanat-2 and Hiomt-2 transcripts in liver and hindgut, suggesting a local melatonin synthesis in goldfish. Moreover, the analysis of daily expression of gAanat-2 under different lighting conditions, including continuous light (24L) and darkness (24D) revealed light-dependent rhythms in the pineal and retina, as expected, but also in liver and hindgut. The persistence in hindgut of these gAanat-2 rhythms under both constant conditions, 24L and 24D, suggests expression of this transcript is governed by a circadian clock and entrained by nonphotic cues. Finally, the current results support the existence of melatonin synthesis in gut and liver of the goldfish. (Author correspondence: mjdelgad@bio.ucm.es)
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