Cohort Profile: Design and methods of the PREDIMED-Plus randomized trial
The PREDIMED (in Spanish: PREvención con DIeta MEDiterránea) primary prevention trial1–3 reported in 2013 that long-term adherence to an energy-unrestricted Mediterranean diet (MedDiet), supplemented with either extra-virgin olive oil (EVOO) or nuts, reduced cardiovascular disease (CVD). PREDIMED showed a 30% relative reduction in the composite cardiovascular primary endpoint (stroke, myocardial infarction or cardiovascular death).2,,3 However, the PREDIMED trial tested only the composition of the diet, but did not test other lifestyle interventions (i.e. energy reduction, increased physical activity (PA) and behavioural modification) frequently applied in the context of the current unprece…
Mediterranean Diet Maintained Platelet Count within a Healthy Range and Decreased Thrombocytopenia-Related Mortality Risk: A Randomized Controlled Trial
There is little information on the dietary modulation of thrombosis-related risk factors such as platelet count. We aimed to assess the effects of Mediterranean diet (MedDiet) on platelet count and related outcomes in an older population at high cardiovascular risk. In participants of the PREDIMED (PREvención con DIeta MEDiterránea) study, we assessed whether an intervention with a MedDiet enriched with extra-virgin olive oil or nuts, relative to a low-fat control diet, modulated platelet count (n = 4189), the risk of developing thrombocytosis and thrombocytopenia (n = 3086), and the association between these alterations and all-cause mortality (median follow-up time: 3.0 years). Although p…
Leisure time physical activity is associated with improved HDL functionality in high cardiovascular risk individuals: a cohort study.
Abstract Aims Physical activity has consistently been shown to improve cardiovascular health and high-density lipoprotein-cholesterol levels. However, only small and heterogeneous studies have investigated the effect of exercise on high-density lipoprotein functions. Our aim is to evaluate, in the largest observational study to date, the association between leisure time physical activity and a range of high-density lipoprotein functional traits. Methods The study sample consisted of 296 Spanish adults at high cardiovascular risk. Usual leisure time physical activity and eight measures of high-density lipoprotein functionality were averaged over two measurements, one year apart. Multivariabl…
Increased Consumption of Virgin Olive Oil, Nuts, Legumes, Whole Grains, and Fish Promotes HDL Functions in Humans
[Scope] To evaluate whether increases in the consumption of cardioprotective food groups (virgin olive oil, nuts, fruits/vegetables, legumes, whole grains, fish, and wine) are associated with improvements in high‐density lipoprotein (HDL) functions in high cardiovascular risk subjects.
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 increas…
Role of HDL function and LDL atherogenicity on cardiovascular risk: a comprehensive examination
[Background] High-density lipoprotein (HDL) functionality and low-density lipoprotein (LDL) atherogenic traits can describe the role of both particles on cardiovascular diseases more accurately than HDL- or LDL-cholesterol levels. However, it is unclear how these lipoprotein properties are particularly affected by different cardiovascular risk factors.
The Mediterranean Diet decreases LDL atherogenicity in high cardiovascular risk individuals: a randomized controlled trial.
cope Traditional Mediterranean diet (TMD) protects against cardiovascular disease through several mechanisms such as decreasing LDL cholesterol levels. However, evidence regarding TMD effects on LDL atherogenic traits (resistance against oxidation, size, composition, cytotoxicity) is scarce. Methods and results We assessed the effects of a 1-year intervention with a TMD on LDL atherogenic traits in a random sub-sample of individuals from the PREDIMED study (N = 210). We compared two TMDs: one enriched with virgin olive oil (TMD-VOO, N = 71) and another with nuts (TMD-Nuts, N = 68), versus a low-fat control diet (N = 71). After the TMD-VOO intervention, LDL resistance against oxidation incre…
Energy Balance and Risk of Mortality in Spanish Older Adults
Clinical data on the direct health effects of energy deficit or surplus beyond its impact on body weight are scarce. We aimed to assess the association with all-cause, cardiovascular and cancer mortality of (1) sustained energy deficit or surplus, calculated according to each individual’s en-ergy intake (EI) and theoretical energy expenditure (TEE), and (2) mid-term change in total EI in a prospective study. In 7119 participants in the PREDIMED Study (PREvención con DIeta MEDi-terránea) with a mean age of 67 years, energy intake was derived from a 137-item food frequency questionnaire. TEE was calculated as a function of age, sex, height, body weight and physical ac-tivity. The main exposur…
Dose-dependent metabolic disposition of hydroxytyrosol and formation of mercapturates in rats
Hydroxytyrosol (HT), one of the major polyphenols present in olive oil, is known to possess a high antioxidant capacity. The aim of the present study was to investigate dose dependent (0, 1, 10 and 100 mg/kg) alterations in the metabolism of HT in rats since it has been reported that metabolites may contribute to biological effects. Special attention was paid to the activation of the semiquinone quinone oxidative cycle and the formation of adducts with potential deleterious effects. Thus, we developed a novel analytical methodology to monitor the in vivo formation of the HT mercapturate, N-acetyl-5-S-cysteinyl-hydroxytyrosol in urine samples. Biomarkers of hepatic and renal toxicity were ev…
Cancer Signaling Transcriptome Is Upregulated in Type 2 Diabetes Mellitus
We aimed to explore the differences in the whole transcriptome of peripheral blood mononuclear cells between elderly individuals with and without type 2 diabetes (T2D). We conducted a microarray-based transcriptome analysis of 19 individuals with T2D and 15 without. Differentially expressed genes according to linear models were submitted to the Ingenuity Pathway Analysis system to conduct a functional enrichment analysis. We established that diseases, biological functions, and canonical signaling pathways were significantly associated with T2D patients when their logarithms of Benjamini&ndash
Polyphenol intake and cardiovascular risk in the PREDIMED-Plus trial. A comparison of different risk equations
Abstract Introduction and objectives Quantification of cardiovascular risk has been based on scores such as Framingham, Framingham-REGICOR, SCORE or Life's Simple 7 (LS7). In vitro, animal, and randomized clinical studies have shown that polyphenols may provide benefits to the vascular system and reduce the inflammatory response. However, some clinical-epidemiological studies have yielded inconsistent results. Our aim was to assess the possible association between intake of the various polyphenol classes and established cardiovascular scores. Methods This cross-sectional analysis involved 6633 PREDIMED-Plus study participants. Food polyphenol content was estimated by a semiquantitative food…
A lifestyle intervention with an energy-restricted Mediterranean diet and physical activity enhances HDL function: a substudy of the PREDIMED-Plus randomized controlled trial
Background Consumption of a Mediterranean diet, adequate levels of physical activity, and energy-restricted lifestyle interventions have been individually associated with improvements in HDL functions. Evidence of intensive interventions with calorie restriction and physical activity is, however, scarce. Objectives To determine whether an intensive lifestyle intervention with an energy-restricted Mediterranean diet plus physical activity enhanced HDL function compared to a non-hypocaloric Mediterranean eating pattern without physical activity. Methods In 391 older adults with metabolic syndrome (mean age, 65 years; mean BMI, 33.3 kg/m2) from 1 of the Prevencion con Dieta Mediterranea-Plus t…
Transcriptional response to a Mediterranean diet intervention exerts a modulatory effect on neuroinflammation signaling pathway.
Background: The Traditional Mediterranean Diet (TMD) is known to have beneficial effects on several chronic diseases. However, data concerning the whole transcriptome modulation of the TMD are scar...
High Fruit and Vegetable Consumption and Moderate Fat Intake Are Associated with Higher Carotenoid Concentration in Human Plasma
This research was funded by CICYT [AGL2016-75329-R] and CIBEROBN from the Instituto de Salud Carlos III, ISCIII from the Ministerio de Ciencia, Innovación y Universidades, (AEI/FEDER, UE), Generalitat de Catalunya (GC) [2017SGR196]. The PREDIMED-Plus trial was supported by the official Spanish Institutions for funding scientific biomedical research, CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn) and Instituto de Salud Carlos III (ISCIII), through the Fondo de Investigación para la Salud (FIS), which is co-funded by the European Regional Development Fund (four coordinated Fondo de Investigaciones Sanitarias projects lead by J.S.-S. and J.V., including the following projects: PI13…
Associations between dietary polyphenols and type 2 diabetes in a cross-sectional analysis of the PREDIMED-Plus Trial: role of body mass index and sex
Overweight and obesity are important risk factors for type 2 diabetes (T2D). Moving towards healthier diets, namely, diets rich in bioactive compounds, could decrease the odds of suffering T2D. However, those individuals with high body mass index (BMI) may have altered absorption or metabolism of some nutrients and dietary components, including polyphenols. Therefore, we aimed to assess whether high intakes of some classes of polyphenols are associated with T2D in a population with metabolic syndrome and how these associations depend on BMI and sex. This baseline cross-sectional analysis includes 6633 participants from the PREDIMED-Plus trial. Polyphenol intakes were calculated from food fr…
Mediterranean Diet and atherothrombosis biomarkers: a randomized controlled trial
Scope To assess whether following a Mediterranean diet (MedDiet) improves atherothrombosis biomarkers in high cardiovascular risk individuals. Methods and results In 358 random volunteers from the PREvención con DIeta MEDiterránea trial, the 1‐year effects on atherothrombosis markers of an intervention with MedDiet, enriched with virgin olive oil (MedDiet‐VOO; n = 120) or nuts (MedDiet‐Nuts; n = 119) versus a low‐fat control diet (n = 119), and whether large increments in MedDiet adherence (≥3 score points, versus compliance decreases) and intake changes in key food items are associated with 1‐year differences in biomarkers. Differences are observed between 1‐year changes in the MedDiet‐VOO…
Fruit and Vegetable Consumption is Inversely Associated with Plasma Saturated Fatty Acids at Baseline in Predimed Plus Trial
I.D.-L. is supported by the [FI_B 00256] from the FI-AGAUR Research Fellowship Program, Generalitat de Catalunya and M.M.-M is supported by the FPU17/00513 grant. a.-H. is supported by the [CD17/00122] grant and S.K.N. is supported by a Canadian Institutes of Health Research (CIHR) Fellowship. We also thank all the volunteers for their participation in and the personnel for their contribution to the PREDIMED-Plus trial. This research was funded by CiCYT [AGL2016-75329-R] and CIBEROBN from the Instituto de Salud Carlos III, ISCIII from the Ministerio de Ciencia, Innovacion y Universidades, (AEI/FEDER, UE), Generalitat de Catalunya (GC) [2017SGR196]. The PREDIMED-Plus trial was supported by t…
Mediterranean Diet and White Blood Cell Count—A Randomized Controlled Trial
We aimed to assess the effects of the antioxidant-rich Mediterranean diet (MedDiet) on white blood cell count. Our study population included participants in the PREvención con DIeta MEDiterránea study (average age 67 years old, 58% women, high cardiovascular risk). We assessed whether a MedDiet intervention enriched in extra-virgin olive oil or nuts, versus a low-fat control diet, modified the incidence of leukocytosis (>
Mediterranean diet and quality of life: Baseline cross-sectional analysis of the PREDIMED-PLUS trial
We assessed if a 17-item score capturing adherence to a traditional Mediterranean diet (MedDiet) was associated with better health-related quality of life among older Spanish men and women with overweight or obesity harboring the metabolic syndrome. We analyzed baseline data from 6430 men and women (age 55-70 years) participating in the PREDIMED-Plus study. PREDIMED-Plus is a multi-centre randomized trial testing an energy-restricted MedDiet combined with promotion of physical activity and behavioral therapy for primary cardiovascular prevention compared to a MedDiet alone. Participants answered a 36-item questionnaire about health-related quality of life (HRQoL) and a 17-item questionnaire…
Dietary Polyphenol Intake is Associated with HDL-Cholesterol and A Better Profile of other Components of the Metabolic Syndrome: A PREDIMED-Plus Sub-Study
Dietary polyphenol intake is associated with improvement of metabolic disturbances. The aims of the present study are to describe dietary polyphenol intake in a population with metabolic syndrome (MetS) and to examine the association between polyphenol intake and the components of MetS. This cross-sectional analysis involved 6633 men and women included in the PREDIMED (PREvenció
Association Between Lifestyle and Hypertriglyceridemic Waist Phenotype in the PREDIMED-Plus Study.
Objective: The hypertriglyceridemic waist (HTGW) phenotype is characterized by abdominal obesity and high levels of triglycerides. In a cross-sectional assessment of PREDIMED-Plus trial participants at baseline, HTGW phenotype prevalence was evaluated, associated risk factors were analyzed, and the lifestyle of individuals with metabolic syndrome and HTGW was examined. Methods: A total of 6,874 individuals aged 55 to 75 with BMI ≥ 27 and < 40 kg/m2 were included and classified by presence (HTGW+ ) or absence (HTGW- ) of HTGW (waist circumference: men ≥ 102 cm, women ≥ 88 cm; fasting plasma triglycerides ≥ 150 mg/dL). Analytical parameters and lifestyle (energy intake and expenditure) were a…
Mediterranean Diet Improves High-Density Lipoprotein Function in High-Cardiovascular-Risk Individuals: A Randomized Controlled Trial.
Background: The biological functions of high-density lipoproteins (HDLs) contribute to explaining the cardioprotective role of the lipoprotein beyond quantitative HDL cholesterol levels. A few small-scale interventions with a single antioxidant have improved some HDL functions. However, to date, no long-term, large-scale, randomized controlled trial has been conducted to assess the effects of an antioxidant-rich dietary pattern (such as a traditional Mediterranean diet [TMD]) on HDL function in humans. Methods: This study was performed in a random subsample of volunteers from the PREDIMED Study (Prevención con Dieta Mediterránea; n=296) after a 1-year intervention. We compared the effects …
Dysfunctional High-Density Lipoproteins Are Associated With a Greater Incidence of Acute Coronary Syndrome in a Population at High Cardiovascular Risk
Background: Studies have failed to establish a clear link between high-density lipoprotein (HDL) cholesterol and cardiovascular disease, leading to the hypothesis that the atheroprotective role of HDL lies in its biological activity rather than in its cholesterol content. However, to date, the association between HDL functional characteristics and acute coronary syndrome has not been investigated comprehensively. Methods: We conducted a case-control study nested within the PREDIMED (Prevención con Dieta Mediterránea) cohort, originally a randomized trial in which participants followed a Mediterranean or low-fat diet. Incident acute coronary syndrome cases (N=167) were individually matched …
Mediterranean Diet Decreases the Initiation of Use of Vitamin K Epoxide Reductase Inhibitors and Their Associated Cardiovascular Risk: A Randomized Controlled Trial
Our aim is to assess whether following a Mediterranean Diet (MedDiet) decreases the risk of initiating antithrombotic therapies and the cardiovascular risk associated with its use in older individuals at high cardiovascular risk. We evaluate whether participants of the PREvenció
Mediterranean diet and antihypertensive drug use: a randomized controlled trial
Objective To examine in older individuals at high cardiovascular risk whether following a Mediterranean diet decreased the necessity of antihypertensive drugs and modulated their associated cardiovascular risk. Methods In the PREvencion con DIeta MEDiterranea study, we assessed whether volunteers randomly allocated to an intervention with a Mediterranean diet enriched with extra-virgin olive oil or nuts (relative to a low-fat control diet) disclosed differences in the risk of: initiating antihypertensive medication in nonusers at baseline (n = 2188); and escalating therapy in participants using one, two, or three drugs at baseline (n = 2361, n = 1579, and n = 554, respectively). We also ass…