Polymorphisms Cyclooxygenase-2 -765G>C and Interleukin-6 -174G>C Are Associated with Serum Inflammation Markers in a High Cardiovascular Risk Population and Do Not Modify the Response to a Mediterranean Diet Supplemented with Virgin Olive Oil or Nuts

Abstract Background/Introduction Microvesicles (MV) are small phospholipid-rich vesicles released into blood by cells that are either damaged, activated or apoptotic. MV participate in diverse functions and also can serve as biomarkers of ongoing cardiovascular cell instability and disease (CVD). Diet is one of cornerstones for CVD prevention, and the effects of diet on MV shedding are poorly characterized. Purpose We aimed at investigating the long term effects of a mediterranean diet compared to a low fat diet (LFD) in MV shedding by cells of the vascular compartment in asymptomatic but high cardiovascular risk patients treated as per guidelines. Methods A total of 155 patients with diabetes or >3 cardiovascular risk factors but free of cardiovascular event were included in the study, consisting in a 3-arm randomized clinical trial. The interventions were as follows: a mediterranean diet supplemented with extra-virgin olive oil -EVOO- (n=53); a mediterranean diet supplemented with mixed nuts -NUTS- (n=49); and a control diet -LFD- (n=53) for one year. Subjects were matched by age, sex, diabetes and dyslipidaemia. At baseline and after one year follow-up, the number of MV and their phenotypic characteristics were assessed by flow cytometry. Phosphatidylserine exposure by annexin V (AV) binding was assessed and different monoclonal antibodies against characteristic cell epitopes were used to identify parental cell origin. Results The mean patient age was 66 years (50% males). Patients were hypertensive (>75%), diabetics (>50%) and dyslipidemics (>30%). No significant changes were observed after one year follow-up in body weight, body mass index, blood pressure, glucose, triglycerides, total, LDL and HDL cholesterol, medication or physical activity within or among groups of intervention. Total MV (AV+/−) were present in higher concentration than AV+ MV for all analyzed phenotypes and cell origins (P<0.0001, all). After one year follow-up, in the EVOO group there was a significant decrease in the concentration of monocyte-derived (CD14+/AV+, CD14+/CD11a+/AV+) and smooth muscle cell-derived (SMA-α+/AV+) circulating MV. In the NUTS group there was a significant decrease in platelet-derived (PAC-1+/AV+, CD62P+/AV+, and CD61+/AV+) MV, and activated cells-derived (CD142+/AV+, CD11a+/AV+ and CD63+/AV+) MV concentrations. On the other hand, one year of LFD decreased platelet PAC-1+/CD62P+/AV+ and CD61+/AV+ MV release. Interestingly, after one year follow-up PAC-1+/AV+ and CD14+/CD11a+/AV+ MV were significantly different between both mediterranean diets compared to the LFD. Conclusions MV are liquid biopsy biomarkers of vascular- and blood-cell activation and injury, that appear sensitive to modification by diet. Therefore, our results indicate that following a mediterranean diet rich in nuts and EVOO clearly prevent cell activation towards a pro-atherosclerotic phenotype and therefore can delay the development of CV complications. Acknowledgement/Funding IJCI-2015-26358 (GC-B), SAF2016-76819-R (LB) (MINECO); RD16/0011/0018 (LB), CB16/11/0041 (LB) (ISCIII)

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Cardiovascular risk protection from the Mediterranean diet and olive oil. A transcriptomic update in humans

Grasas y Aceites ◽

10.3989/gya.0451161 ◽

2016 ◽

Vol 67 (4) ◽

pp. 161 ◽

Cited By ~ 1

Author(s):

S. Carrión ◽

L. Torres ◽

O. Castañer

Keyword(s):

Cardiovascular Risk ◽

Olive Oil ◽

Mediterranean Diet ◽

Virgin Olive Oil ◽

Real Life ◽

Transcriptomic Response ◽

The Mediterranean ◽

Risk Protection ◽

And Oxidative Stress ◽

Cox 1

This review highlights the human studies that explore the benefits of the Mediterranean diet and olive oil, based on gene expression analysis. We summarized consistent human transcriptomic studies on cardiovascular risk, based on TMD and olive oil interventions, with real life doses and conditions. A literature review was carried out leading up to February 2016. The results show that the TMD, specially supplemented with virgin olive oil, produces beneficial changes in the transcriptomic response of relevant genes in cardiovascular risk such as CAT, GPX1 and SIRT2. p65 and MCP-1, IL1B, IL6, CXCL1, INF-γ, ARHGAP15 and IL7R, which are involved in inflammation; and ABCA1, SR-B1, PPARBP, PPARα, PPARγ, PPARδ, CD-36 and COX-1, which play an important role in cholesterol efflux. The available data illustrate a transcriptomic effect on atherosclerosis, inflammation and oxidative stress pathways as well as the mentioned genes.

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Mediterranean diet modulates the effect of rs1761667 in theCD36gene on FFA concentration and BMI in a high cardiovascular risk population

Endocrine Abstracts ◽

10.1530/endoabs.32.p179 ◽

2013 ◽

Author(s):

Carolina Ortega-Azorin ◽

Diego Godoy ◽

Paula Carrasco ◽

Eva M Asensio ◽

Vicente Zanon-Moreno ◽

...

Keyword(s):

Cardiovascular Risk ◽

Mediterranean Diet ◽

High Cardiovascular Risk ◽

Risk Population

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A Mediterranean Diet Enriched with Olive Oil Is Associated with Higher Serum Total Osteocalcin Levels in Elderly Men at High Cardiovascular Risk

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2012-2221 ◽

2012 ◽

Vol 97 (10) ◽

pp. 3792-3798 ◽

Cited By ~ 49

Author(s):

José Manuel Fernández-Real ◽

Mónica Bulló ◽

José Maria Moreno-Navarrete ◽

Wifredo Ricart ◽

Emilio Ros ◽

...

Keyword(s):

Cardiovascular Risk ◽

Olive Oil ◽

Mediterranean Diet ◽

Elderly Men ◽

High Cardiovascular Risk

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Association between the rs6950982 polymorphism near the SERPINE1 gene and blood pressure and lipid parameters in a high-cardiovascular-risk population: interaction with Mediterranean diet

Genes & Nutrition ◽

10.1007/s12263-012-0327-1 ◽

2012 ◽

Vol 8 (4) ◽

pp. 401-409 ◽

Cited By ~ 6

Author(s):

Mercedes Sotos-Prieto ◽

Marisa Guillén ◽

Olga Portolés ◽

José V. Sorlí ◽

José I. González ◽

...

Keyword(s):

Blood Pressure ◽

Cardiovascular Risk ◽

Mediterranean Diet ◽

High Cardiovascular Risk ◽

Risk Population ◽

Population Interaction ◽

Lipid Parameters

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Anti-inflammatory effects of the Mediterranean diet: the experience of the PREDIMED study

Proceedings of The Nutrition Society ◽

10.1017/s0029665110001539 ◽

2010 ◽

Vol 69 (3) ◽

pp. 333-340 ◽

Cited By ~ 154

Author(s):

Ramon Estruch

Keyword(s):

Risk Factors ◽

Cardiovascular Risk ◽

High Risk ◽

Olive Oil ◽

Mediterranean Diet ◽

Virgin Olive Oil ◽

Inflammatory Biomarkers ◽

Low Fat ◽

Low Fat Diet ◽

Anti Inflammatory

Several epidemiological and clinical studies have evaluated the effects of a Mediterranean diet (Med-Diet) on total cardiovascular mortality, and all concluded that adherence to the traditional Med-Diet is associated with reduced cardiovascular risk. However, the molecular mechanisms involved are not fully understood. Since atherosclerosis is nowadays considered a low-grade inflammatory disease, recent studies have explored the anti-inflammatory effects of a Med-Diet intervention on serum and cellular biomarkers related to atherosclerosis. In a pilot study of the PREvencion con DIeta MEDiterranea (PREDIMED) trial, we analysed the short-term effects of two Med-Diet interventions, one supplemented with virgin olive oil and another with nuts, on vascular risk factors in 772 subjects at high risk for CVD, and in a second study we evaluated the effects of these interventions on cellular and serum inflammatory biomarkers in 106 high-risk subjects. Compared to a low-fat diet, the Med-Diet produced favourable changes in all risk factors. Thus, participants in both Med-Diet groups reduced blood pressure, improved lipid profile and diminished insulin resistance compared to those allocated a low-fat diet. In addition, the Med-Diet supplemented with virgin olive oil or nuts showed an anti-inflammatory effect reducing serum C-reactive protein, IL-6 and endothelial and monocytary adhesion molecules and chemokines, whereas these parameters increased after the low-fat diet intervention. In conclusion, Med-Diets down-regulate cellular and circulating inflammatory biomarkers related to atherogenesis in subjects at high cardiovascular risk. These results support the recommendation of the Med-Diet as a useful tool against CVD.

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Mediterranean Diet Maintained Platelet Count within a Healthy Range and Decreased Thrombocytopenia-Related Mortality Risk: A Randomized Controlled Trial

Nutrients ◽

10.3390/nu13020559 ◽

2021 ◽

Vol 13 (2) ◽

pp. 559

Author(s):

Álvaro Hernáez ◽

Camille Lassale ◽

Sara Castro-Barquero ◽

Emilio Ros ◽

Anna Tresserra-Rimbau ◽

...

Keyword(s):

Platelet Count ◽

Cardiovascular Risk ◽

Mediterranean Diet ◽

Controlled Trial ◽

Control Diet ◽

Virgin Olive Oil ◽

Hazard Ratio ◽

High Cardiovascular Risk ◽

All Cause Mortality ◽

Related Mortality

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 platelet count increased over time (+0.98·109 units/L·year [95% confidence interval: 0.12; 1.84]), MedDiet interventions moderated this increase, particularly in individuals with near-high baseline count (both MedDiets combined: −3.20·109 units/L·year [−5.81; −0.59]). Thrombocytopenia incidence was lower in the MedDiet interventions (incidence rates: 2.23% in control diet, 0.91% in MedDiets combined; hazard ratio: 0.44 [0.23; 0.83]). Finally, thrombocytopenia was associated with a higher risk of all-cause mortality (hazard ratio: 4.71 [2.69; 8.24]), but this relationship was attenuated in those allocated to MedDiet (p-interaction = 0.018). In brief, MedDiet maintained platelet counts within a healthy range and attenuated platelet-related mortality in older adults at high cardiovascular risk.

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Mediterranean Diet Decreases the Initiation of Use of Vitamin K Epoxide Reductase Inhibitors and Their Associated Cardiovascular Risk: A Randomized Controlled Trial

Nutrients ◽

10.3390/nu12123895 ◽

2020 ◽

Vol 12 (12) ◽

pp. 3895

Author(s):

Sara Castro-Barquero ◽

Margarita Ribó-Coll ◽

Camille Lassale ◽

Anna Tresserra-Rimbau ◽

Olga Castañer ◽

...

Keyword(s):

Cardiovascular Risk ◽

Olive Oil ◽

Vitamin K ◽

Cardiovascular Events ◽

Virgin Olive Oil ◽

Extra Virgin Olive Oil ◽

High Cardiovascular Risk ◽

Vitamin K Epoxide Reductase ◽

Reductase Inhibitors ◽

Epoxide Reductase

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 PREvención con DIeta MEDiterránea (PREDIMED) study allocated to a MedDiet enriched in extra-virgin olive oil or nuts (versus a low-fat control intervention) disclose differences in the risk of initiation of: (1) vitamin K epoxide reductase inhibitors (acenocumarol/warfarin; n = 6772); (2) acetylsalicylic acid as antiplatelet agent (n = 5662); and (3) other antiplatelet drugs (cilostazol/clopidogrel/dipyridamole/ditazol/ticlopidine/triflusal; n = 6768). We also assess whether MedDiet modifies the association between the antithrombotic drug baseline use and incident cardiovascular events. The MedDiet intervention enriched with extra-virgin olive oil decreased the risk of initiating the use of vitamin K epoxide reductase inhibitors relative to control diet (HR: 0.68 [0.46–0.998]). Their use was also more strongly associated with an increased risk of cardiovascular disease in participants not allocated to MedDiet interventions (HRcontrol diet: 4.22 [1.92–9.30], HRMedDiets: 1.71 [0.83–3.52], p-interaction = 0.052). In conclusion, in an older population at high cardiovascular risk, following a MedDiet decreases the initiation of antithrombotic therapies and the risk of suffering major cardiovascular events among users of vitamin K epoxide reductase inhibitors.

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Mediterranean Diet and atherothrombosis biomarkers: a randomized controlled trial

10.1101/19001909 ◽

2019 ◽

Author(s):

Álvaro Hernáez ◽

Olga Castañer ◽

Anna Tresserra-Rimbau ◽

Xavier Pintó ◽

Montserrat Fitó ◽

...

Keyword(s):

Cardiovascular Risk ◽

Fatty Acid ◽

Mediterranean Diet ◽

Controlled Trial ◽

Control Diet ◽

Virgin Olive Oil ◽

High Density Lipoproteins ◽

Low Fat ◽

High Cardiovascular Risk ◽

Platelet Factor

ABSTRACTScopeTo assess whether following a Mediterranean diet (MedDiet) improves atherothrombosis biomarkers in high cardiovascular risk individuals.Methods and resultsIn 358 random volunteers from the PREDIMED trial (Prevención con Dieta Mediterránea), we assessed 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). In a secondary, observational approach, we studied whether volunteers with large increments in MedDiet adherence (>2 score points) were associated with 1-year improvements in biomarkers (relative to those worsening their adherence). The MedDiet-VOO intervention increased platelet activating factor-acetylhydrolase activity in high-density lipoproteins (HDLs) by 7.5% [95% confidence interval: 0.17; 14.8] and decreased HDL-bound α1-antitrypsin levels by 6.1% [−11.8; −0.29]. The MedDiet-Nuts one reduced non-esterified fatty acid concentrations by 9.3% [−18.1; −0.53]. Only the low-fat diet was associated with increases in platelet factor-4 and prothrombin factor1+2 levels versus baseline (P=0.012 and P=0.003, respectively, according to Wilcoxon signed-rank tests). Finally, large MedDiet increments were associated with less fibrinogen (−9.5% [−18.3; −0.60]) and non-esterified fatty acid concentrations (−16.7% [−31.7; −1.74]).ConclusionFollowing a MedDiet improves atherothrombosis biomarkers in high cardiovascular risk individuals.

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