Mediterranean diet as a strategy for preserving kidney function in patients with coronary heart disease with type 2 diabetes and obesity: a secondary analysis of CORDIOPREV randomized controlled trial.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is recognized an independent risk factor for chronic kidney disease (CKD). The precise contribution and differential response to treatment strategies to reduce kidney dysfunction, depending on whether obesity is present alongside T2DM or not, remain to be fully clarified. Our objective was to improve our understanding of how obesity contributes to kidney function in patients with T2DM and coronary heart disease (CHD), who are highly predisposed to CKD, to assign the most effective dietary approach to preserve kidney function. METHODS: 1002 patients with CHD and estimated glomerular filtration rate (eGFR)≥30 ml/min/1.73m2, were randomized to consume a Mediterranean diet (35% fat, 22% MUFA, < 50% carbohydrates) or a low-fat diet (28% fat, 12% MUFA, > 55% carbohydrates). Patients were classified into four groups according to the presence of T2DM and/or obesity at baseline: Non-Obesity/Non-T2DM, Obesity/Non-T2DM, Non-Obesity/T2DM and Obesity/T2DM. We evaluated kidney function using serum creatinine-based estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratio (uACR) before and after 5-years of dietary intervention. RESULTS: Patients with Obesity/T2DM had the lowest baseline eGFR and the highest baseline uACR compared to non-diabetics (p < 0.05). After dietary intervention, the Mediterranean diet induced a lower eGFR decline in patients with Obesity/T2DM, compared to a low-fat diet but not in the other groups (p = 0.014). The Mediterranean diet, but not the low-fat diet, also reduced uACR only in patients with Obesity/T2DM (p = 0.024). CONCLUSIONS: Obesity provided an additive effect to T2DM resulting in a more pronounced decline in kidney function compared to T2DM alone when compared to non-diabetics. In patients with concomitant presence of T2DM and obesity, with more metabolic complications, consumption of a Mediterranean diet seemed more beneficial than a low-fat diet in terms of preserving kidney function. These findings provide valuable insights for tailoring personalized lifestyle modifications in secondary prevention of cardiovascular disease. TRIAL REGISTRATION: URL, http://www.cordioprev.es/index.php/en . CLINICALTRIALS: gov number, NCT00924937.

QuantiFERON-CMV assay by chemiluminescence immunoassay: Is it more suitable for real-live monitoring of transplant patients?

BACKGROUND: The QuantiFERONCMV (QF-CMV) assay is an interferon-gamma release assay (IGRA) used to monitor CMV-specific cell-mediated immunity (CMV-CMI) by ELISA in transplant patients. However, a chemiluminescent immunoassay (CLIA) has been developed to quantify IFNG in the QuantiFERON-Tuberculosis (TB) to detect latent TB infection. OBJECTIVES: The aim of this work is to compare the results of QF-CMV by ELISA with those obtained by CLIA in an automated Liaison XL analyzer using the QuantiFERON-TB Gold Plus reagents. STUDY DESIGN: The QF-CMV assay had been performed by ELISA in kidney and lung transplant patients between July 2019-April 2023 at the IMIBIC/Reina Sofía Hospital (Cordoba, Spain). The remaining QF-CMV supernatants had been preserved at -80 ºC from then. Now, the IFNG levels in the same samples were determined by CLIA. RESULTS: One hundred and three QF-CMV supernatants from kidney (n = 50) and lung (n = 53) transplant patients were selected. An agreement of 87.4 % (kappa coefficient 0.788) between CLIA and ELISA was observed. Thirteen (12.6 %) discrepant results were detected. Some Indeterminate results by ELISA converted to Non-reactive by CLIA (0.53-0.92 IU/mL for Mitogen-Nil values). Likewise, borderline Non-reactive results by ELISA were above the 0.2 IU/mL cut-off by CLIA and then were Reactive (0.21-0.31 for CMV-Nil values). CONCLUSION: CLIA shows substantial concordance with ELISA and acceptable discrepancies. The possible higher sensitivity of CLIA returns a higher number of Reactive results, which entails potential clinical consequences. Therefore, a new threshold to confer protection against CMV infection after transplantation needs to be defined.

Diet and SIRT1 Genotype Interact to Modulate Aging-Related Processes in Patients with Coronary Heart Disease: From the CORDIOPREV Study.

We investigated whether long-term consumption of two healthy diets (low-fat (LF) or Mediterranean (Med)) interacts with SIRT1 genotypes to modulate aging-related processes such as leucocyte telomere length (LTL), oxidative stress (OxS) and inflammation in patients with coronary heart disease (CHD). LTL, inflammation, OxS markers (at baseline and after 4 years of follow-up) and SIRT1-Single Nucleotide Polymorphisms (SNPs) (rs7069102 and rs1885472) were determined in patients from the CORDIOPREV study. We analyzed the genotype-marker interactions and the effect of diet on these interactions. Regardless of the diet, we observed LTL maintenance in GG-carriers for the rs7069102, in contrast to carriers of the minor C allele, where it decreased after follow-up (p = 0.001). The GG-carriers showed an increase in reduced/oxidized glutathione (GSH/GSSG) ratio (p = 0.003), lower lipid peroxidation products (LPO) levels (p < 0.001) and a greater decrease in tumor necrosis factor-alpha (TNF-α) levels (p < 0.001) after follow-up. After the LF diet intervention, the GG-carriers showed stabilization in LTL which was significant compared to the C allele subjects (p = 0.037), although the protective effects found for inflammation and OxS markers remained significant after follow-up with the two diets. Patients who are homozygous for the SIRT1-SNP rs7069102 (the most common genotype) may benefit from healthy diets, as suggested by improvements in OxS and inflammation in patients with CHD, which may indicate the slowing-down of the aging process and its related diseases.

A Gene Variation at the ZPR1 Locus (rs964184) Interacts With the Type of Diet to Modulate Postprandial Triglycerides in Patients With Coronary Artery Disease: From the Coronary Diet Intervention With Olive Oil and Cardiovascular Prevention Study.

Background and Aims: rs964184 variant in the ZPR1 gene has been associated with blood lipids levels both in fasting and postprandial state and with the risk of myocardial infarction in high-risk cardiovascular patients. However, whether this association is modulated by diet has not been studied. Objective: To investigate whether the type of diet (low-fat or Mediterranean diets) interacts with genetic variability at this loci to modulate fasting and postprandial lipids in coronary patients. Materials and Methods: The genotype of the rs964184 polymorphism was determined in the Cordioprev Study population (NCT00924937). Fasting and Postprandial triglycerides were assessed before and after 3 years of dietary intervention with either a Mediterranean or a low-fat diet. Postprandial lipid assessment was done by a 4-h oral fat tolerance test (OFTT). Differences in triglycerides levels were identified using repeated-measures ANCOVA. Results: From 523 patients (85% males, mean age 59 years) that completed the OFTT at baseline and after 3 years of intervention and had complete genotype information, 125 of them were carriers of the risk allele G. At the start of the study, these patients showed a higher fasting and postprandial triglycerides (TG) plasma levels. After 3 years of dietary intervention, G-carriers following a Mediterranean Diet maintained higher fasting and postprandial triglycerides, while those on the low-fat diet reduced their postprandial triglycerides to similar values to the population without the G-allele. Conclusion: After 3 years of dietary intervention, the altered postprandial triglyceride response induced by genetic variability in the rs964184 polymorphism of the ZPR1 gene can be modulated by a low-fat diet, better than by a Mediterranean diet, in patients with coronary artery disease.

Long-term secondary prevention of cardiovascular disease with a Mediterranean diet and a low-fat diet (CORDIOPREV): a randomised controlled trial.

BACKGROUND: Mediterranean and low-fat diets are effective in the primary prevention of cardiovascular disease. We did a long-term randomised trial to compare the effects of these two diets in secondary prevention of cardiovascular disease. METHODS: The CORDIOPREV study was a single-centre, randomised clinical trial done at the Reina Sofia University Hospital in Córdoba, Spain. Patients with established coronary heart disease (aged 20-75 years) were randomly assigned in a 1:1 ratio by the Andalusian School of Public Health to receive a Mediterranean diet or a low-fat diet intervention, with a follow-up of 7 years. Clinical investigators (physicians, investigators, and clinical endpoint committee members) were masked to treatment assignment; participants were not. A team of dietitians did the dietary interventions. The primary outcome (assessed by intention to treat) was a composite of major cardiovascular events, including myocardial infarction, revascularisation, ischaemic stroke, peripheral artery disease, and cardiovascular death. This study is registered with ClinicalTrials.gov, NCT00924937. FINDINGS: From Oct 1, 2009, to Feb 28, 2012, a total of 1002 patients were enrolled, 500 (49·9%) in the low-fat diet group and 502 (50·1%) in the Mediterranean diet group. The mean age was 59·5 years (SD 8·7) and 827 (82·5%) of 1002 patients were men. The primary endpoint occurred in 198 participants: 87 in the Mediterranean diet group and 111 in the low-fat group (crude rate per 1000 person-years: 28·1 [95% CI 27·9-28·3] in the Mediterranean diet group vs 37·7 [37·5-37·9] in the low-fat group, log-rank p=0·039). Multivariable-adjusted hazard ratios (HRs) of the different models ranged from 0·719 (95% CI 0·541-0·957) to 0·753 (0·568-0·998) in favour of the Mediterranean diet. These effects were more evident in men, with primary endpoints occurring in 67 (16·2%) of 414 men in the Mediterranean diet group versus 94 (22·8%) of 413 men in the low-fat diet group (multiadjusted HR 0·669 [95% CI 0·489-0·915], log-rank p=0·013), than in 175 women for whom no difference was found between groups. INTERPRETATION: In secondary prevention, the Mediterranean diet was superior to the low-fat diet in preventing major cardiovascular events. Our results are relevant to clinical practice, supporting the use of the Mediterranean diet in secondary prevention. FUNDING: Fundacion Patrimonio Comunal Olivarero; Fundacion Centro para la Excelencia en Investigacion sobre Aceite de Oliva y Salud; local, regional, and national Spanish Governments; European Union.

Diabetes Remission Is Modulated by Branched Chain Amino Acids According to the Diet Consumed: From the CORDIOPREV Study.

SCOPE: Branched Chain Amino Acids (BCAA) plasma levels may be differentially associated with type 2 diabetes mellitus (T2DM) remission through the consumption of the Mediterranean diet (Med) and a low-fat (LF) diet. METHODS: One hundred eighty-three newly diagnosed T2DM patients within the CORDIOPREV study are randomized to consume the Med or a LF diet. BCAA plasma levels (isoleucine, leucine, and valine) are measured at fasting and after 120 min of an oral glucose tolerance test (OGTT) at the baseline of the study and after 5 years of the dietary intervention. RESULTS: Isoleucine, leucine, and valine plasma levels after 120 min of an OGTT in the Med diet (N = 80) are associated by COX analysis with T2DM remission: HR per SD (95% CI): 0.53 (0.37-0.77), 0.75 (0.52-1.08), and 0.61 (0.45-0.82), respectively; no association is found in patients who consumed a LF diet (N = 103). BCAA plasma levels combined in a score show a HR of 3.33 (1.55-7.19) of T2DM remission for patients with a high score values in the Med diet, while in those with a LF diet, no association is found. CONCLUSION: The study suggests that BCAA measurements potentially be used as a tool to select the most suitable diet to induce T2DM remission by nutritional strategies.

A plasma fatty acid profile associated to type 2 diabetes development: from the CORDIOPREV study.

PURPOSE: The prevalence of type 2 diabetes mellitus (T2DM) is increasing worldwide. For this reason, it is essential to identify biomarkers for the early detection of T2DM risk and/or for a better prognosis of T2DM. We aimed to identify a plasma fatty acid (FA) profile associated with T2DM development. METHODS: We included 462 coronary heart disease patients from the CORDIOPREV study without T2DM at baseline. Of these, 107 patients developed T2DM according to the American Diabetes Association (ADA) diagnosis criteria after a median follow-up of 60 months. We performed a random classification of patients in a training set, used to build a FA Score, and a Validation set, in which we tested the FA Score. RESULTS: FA selection with the highest prediction power was performed by random survival forest in the Training set, which yielded 4 out of the 24 FA: myristic, petroselinic, α-linolenic and arachidonic acids. We built a FA Score with the selected FA and observed that patients with a higher score presented a greater risk of T2DM development, with an HR of 3.15 (95% CI 2.04-3.37) in the Training set, and an HR of 2.14 (95% CI 1.50-2.84) in the Validation set, per standard deviation (SD) increase. Moreover, patients with a higher FA Score presented lower insulin sensitivity and higher hepatic insulin resistance (p < 0.05). CONCLUSION: Our results suggest that a detrimental FA plasma profile precedes the development of T2DM in patients with coronary heart disease, and that this FA profile can, therefore, be used as a predictive biomarker. CLINICAL TRIALS.GOV. IDENTIFIER: NCT00924937.

Chronodisruption and diet associated with increased cardiometabolic risk in coronary heart disease patients: the CORDIOPREV study.

Individuals with evening chronotypes are prone to suffer chronodisruption and display worse lifestyle habits than morning-types, exhibiting higher cardiovascular diseases (CVD). However, it is unknown whether CVD patients, who are evening chronotypes, have higher cardiometabolic risk than morning-types. This study explored whether individual chronotypes were associated with cardiometabolic risk in patients from the CORDIOPREV study (n = 857). We also investigated whether potential associations were moderated by long-term consumption of two healthy diets (Mediterranean and Low-fat diets). This population was classified into chronotypes using the Morningness-Eveningness Questionnaire. Seven-day daily rhythms in wrist temperature (T), rest-activity (A) and position (P) were recorded in a subset of patients (n = 168), and an integrative variable TAP was determined. Metabolic Syndrome (MetS) was determined at baseline, and metabolic and inflammation markers were measured at baseline and yearly during the 4 years of follow-up. Differences in several lifestyle factors were analyzed according to chronotype. At all times, evening-types had higher triglycerides, C-reactive protein and homocysteine and lower high density lipoprotein cholesterol than morning-types (P < 0.05). Evening-types had a higher prevalence of MetS (OR 1.58 IC 95% [1.10 - 2.28], P = 0.01). Moreover, they were more sedentary, displayed less and delayed physical activity and ate and slept later. In addition, evening-types had lower amplitude, greater fragmentation, lower robustness and less stable circadian pattern at TAP (P < 0.01), all related to a less healthy circadian pattern. In conclusion, evening-types with CVD had higher cardiometabolic risk and less robust circadian-related rhythms than morning-types, regardless of the nutritional intervention.

Influence of dietary intervention on microvascular endothelial function in coronary patients and atherothrombotic risk of recurrence.

Endothelial dysfunction is a key player in both the onset and development of atherosclerosis. No study has examined whether healthy dietary patterns can improve microvascular endothelial function in patients with coronary heart disease (CHD) in the long-term and whether this relationship can affect patient's risk of CHD recurrence. In the CORDIOPREV study, a randomized, double-blind, controlled trial, dietary intervention with either the Mediterranean diet or a low-fat diet was implemented in 1,002 CHD patients. A laser-doppler flowmetry was performed at baseline and after 6 years of follow up in 664 patients, evaluating the effects of this dietary intervention on microvascular basal flow and reactive hyperaemia area, as well as on the risk of CHD recurrence, based on the TRS2P risk score. Basal flow (97.78 ± 2.79 vs. 179.31 ± 5.06 arbitrary perfusion units, 83.38% increase, p < 0.001) and reactive hyperaemia area (4233.3 ± 127.73 vs. 9695.9 ± 205.23 arbitrary perfusion units per time, 129.04% increase, p < 0.001) improved after the dietary intervention in the cohort, without finding differences due to the diet (p > 0.05 for the diet-effect). When patients were stratified to low, moderate or high-risk of recurrence, basal flow was similarly increased in all three groups. However, reactive hyperaemia area was improved to a greater extent in patients at the low-risk group compared with those at moderate or high-risk. No differences were observed between diets. Healthy dietary patterns can improve microvascular endothelial function and this improvement persists in the long-term. Patients with a low-risk of CHD recurrence show a greater improvement in reactive vasodilation to ischemia than patients in the moderate or high-risk groups.

MiRNAs profile as biomarkers of nutritional therapy for the prevention of type 2 diabetes mellitus: From the CORDIOPREV study.

BACKGROUND AND AIM: The incidence of type 2 diabetes mellitus (T2DM) has increased worldwide. One of the first actions to reduce the risk of this disease is to implement healthy dietary models; however, no universal dietary strategies have so far been established. In addition, MicroRNAs (miRNAs) are emerging as new biomarkers to predict disease. We aimed to study whether miRNAs could be used to select the nutritional therapy to prevent T2DM development in patients with cardiovascular disease. METHODS: All patients from the CORDIOPREV study without T2DM at baseline according to the American Diabetes Association (ADA) diagnostic criteria (n = 462) were included in the present study. Of them, after a median dietary intervention period of 60 months with two diets (Low fat or Mediterranean diets), 107 developed T2DM and 355 subjects did not develop the disease. The plasma levels of 24 miRNAs were measured at baseline by qRT-PCR. The risk of T2DM was evaluated by Cox regression analysis based on the plasma levels of the miRNAs at baseline and according to the dietary intervention. Finally, pathways analyses were carried out to identify target genes regulated by the miRNAs studied and cellular processes which could be associated with T2DM development. RESULTS: Cox regression analyses showed that patients with low plasma levels of miR-145 at baseline showed a higher risk of developing T2DM after consumption of an LFHCC diet. In addition, patients with low levels of miR-29a, miR-28-3p and miR-126 and high plasma levels of miR-150 at baseline showed a higher risk of developing T2DM after consumption of the Med diet. Finally, pathways analysis showed an interaction of miR-126 and miR-29a in the modulation of FoxO, TNF-α, PI3K-AKT, p53 and mTOR signaling, associated with T2DM development. CONCLUSION: Our results suggest that circulating miRNAs could be used in clinical practice as a new tool for selecting the most suitable diet to prevent type 2 diabetes mellitus development in patients with cardiovascular disease. CLINICAL TRIALS NUMBER: NCT00924937.

Age-dependent effect of metabolic phenotypes on carotid atherosclerotic disease in coronary heart disease patients (CORDIOPREV study).

BACKGROUND: Aging is associated with a high risk for cardiovascular disease. The relation of obesity and risk of cardiovascular events appears to be more closely linked to certain clinical or metabolic phenotypes than to obesity itself. Our aim was to establish whether aging influenced the metabolic phenotypes regarding to cardiovascular risk, evaluated by changes in the intima media thickness-common carotid (IMT-CC), in coronary heart disease (CHD) patients. METHODS: In this cross-sectional study, 1002 CHD patients were studied at entry from the CORDIOPREV study. We performed carotid ultrasound assessment to obtain their IMT-CC values. Carotid atherosclerosis was considered to exist if IMT-CC > 0.7 mm. RESULTS: Age determined a higher IMT-CC, regardless metabolic phenotype (all p < 0.05). Metabolically healthy non-obese (MHNO) aged< 60 showed a lesser prevalence for carotid atherosclerotic disease than metabolically sick non-obese (MSNO) and obese (MSO), while MHNO aged≥60 only showed less prevalence for the disease than the MSO. Carotid atherosclerosis associated with age, sex, impaired fasting glucose (IFG), hypertension and high sensitivity C-reactive protein (hsCRP). However, in patients aged< 60, it associated with sex and IFG and in the age ≥ 60 group, with hypertension and hsCRP. CONCLUSIONS: Our results suggest that CHD patients aged≥60 are less metabolic flexible compared to patients aged< 60. Thus, MHO patients aged≥60 show the same risk of suffering carotid atherosclerosis as those with metabolic disease, while MHO patients aged< 60 show lower risk than MSO. This fact indicates the need to focus on therapeutic strategies in order to modify those parameters related to obesity and metabolic inflexibility in patients with CHD before entering old age.

Long-term dietary adherence and changes in dietary intake in coronary patients after intervention with a Mediterranean diet or a low-fat diet: the CORDIOPREV randomized trial.

PURPOSE: Adherence to a healthy dietary pattern positively influences clinical outcomes in cardiovascular prevention, but long-term adherence is difficult to maintain. We evaluated 5-year changes in dietary habits, adherence achieved, and its maintenance in a cohort of coronary patients from the CORDIOPREV study. METHODS: 1002 coronary patients were randomized to a Mediterranean diet (n = 502) or a low-fat diet (n = 500) and received individual-group-telephone visits and personalized dietary advice. A validated food-frequency questionnaire, a 14-point Mediterranean diet adherence screener, and a 9-point low-fat diet adherence score were used. Dietary adherence was categorized into Low, Medium, and High Adherence. Changes in nutrient intake, food consumption, and adherence were analyzed on a yearly basis. The maintenance of long-term dietary adherence was evaluated using data after the first year and fifth year. RESULTS: From baseline to 5 years, significant increases were observed in overall dietary adherence (Mediterranean diet from 8.9 to 11.4; low-fat diet from 3.9 to 7.1) and in the percentage of patients considered High Adherence (Mediterranean diet from 41 to 89%; low-fat diet from 4 to 67%). When we evaluated the maintenance of adherence, patients considered Low and Medium Adherence at 1 year increased their adherence at the 5 years with both diets and patients considered High Adherence maintained their adherence with a Mediterranean diet, but decreased their adherence with a low-fat diet. CONCLUSIONS: A comprehensive dietary intervention results in an overall long-term improvement and maintenance of adherence to the Mediterranean and low-fat diets. In our population, the Mediterranean diet group achieved a high level of adherence in the short term which was maintained in the long term.

Beneficial effect of CETP gene polymorphism in combination with a Mediterranean diet influencing lipid metabolism in metabolic syndrome patients: CORDIOPREV study.

The cholesteryl ester transfer protein (CETP) gene has been implicated in high-density lipoprotein (HDL-C) metabolism. However, little is known about the impact of this gene on metabolic syndrome (MetS) patients and its interaction with diet. Here, we evaluate whether the consumption of a Mediterranean diet, compared with a Low-fat diet, interacts with the rs3764261 SNP at the CETP locus to modify lipid metabolism in MetS patients. Plasma lipid concentrations and rs3764261 genotypes were determined in 424 MetS subjects participating in the CORDIOPREV clinical trial (NCT00924937). Gene-diet interactions were analyzed after a year of dietary intervention (Mediterranean diet (35% fat, 22% MUFA) vs Low-fat diet (28% fat, 12% MUFA)). We found significant gene-diet interactions between rs3764261 SNP and the dietary pattern for HDL-C (P = 0.006) and triglyceride concentrations (P = 0.040). Specifically, after 12 months of Mediterranean diet intervention, subjects who were carriers of the minor T allele (TT + TG) displayed higher plasma HDL-C concentrations (P = 0.021) and lower triglycerides (P = 0.020) compared with those who were homozygous for the major allele (GG). In contrast, in the Low-fat intervention group, no significant differences were found between CETP genotypes after 12 months of dietary treatment. Our data support the notion that the consumption of a Mediterranean diet may play a contributing role in triggering lipid metabolism by interacting with the rs3764261 SNP at CETP gene locus in MetS patients. Due to the complex nature of gene-environment interactions, dietary adjustment in MetS patients may require a personalized approach.

Assessment of postprandial triglycerides in clinical practice: Validation in a general population and coronary heart disease patients.

BACKGROUND: Previous studies have suggested that for clinical purposes, subjects with fasting triglycerides (TGs) between 89-180 mg/dl (1-2 mmol/l) would benefit from postprandial TGs testing. OBJECTIVE: To determine the postprandial TG response in 2 independent studies and validate who should benefit diagnostically from an oral-fat tolerance test (OFTT) in clinical practice. METHODS: A population of 1002 patients with coronary heart disease (CHD) from the CORDIOPREV clinical trial and 1115 white US subjects from the GOLDN study underwent OFTTs. Subjects were classified into 3 groups according to fasting cut points of TGs to predict the usefulness of OFTT: (1) TG < 89 mg/dl (<1 mmol/l); (2) TG, 89-180 mg/dl (1-2 mmol/l); and (3) TG > 180 mg/dl (>2 mmol/l). Postprandial TG concentration at any point > 220 mg/dl (>2.5 mmol/l) has been pre-established as an undesirable postprandial response. RESULTS: Of the total, 49% patients with CHD and 42% from the general population showed an undesirable response after the OFTT. The prevalence of undesirable postprandial TG in the CORDIOPREV clinical trial was 12.8, 50.3, and 89.7%, in group 1, 2, and 3, respectively (P < .001) and 11.2, 58.1, and 97.5% in group 1, 2, and 3, respectively (P < .001) in the GOLDN study. CONCLUSIONS: These two studies validate the predictive values reported in a previous consensus. Moreover, the findings of the CORDIOPREV and GOLDN studies show that an OFTT is useful to identify postprandial hyperlipidemia in subjects with fasting TG between 1-2 mmol/l (89-180 mg/dL), because approximately half of them have hidden postprandial hyperlipidemia, which may influence treatment. An OFTT does not provide additional information regarding postprandial hyperlipidemia in subjects with low TG (<1 mmol/l, <89 mg/dL) or increased TG (>2 mmol/l, >180 mg/dl).

TNFA gene variants related to the inflammatory status and its association with cellular aging: From the CORDIOPREV study.

BACKGROUND: Several single nucleotide polymorphisms have been proposed as potential predictors of the development of age-related diseases. OBJECTIVE: To explore whether Tumor Necrosis Factor Alpha (TNFA) gene variants were associated with inflammatory status, thus facilitating the rate of telomere shortening and its relation to cellular aging in a population with established cardiovascular disease from the CORDIOPREV study (NCT00924937). MATERIALS AND METHODS: SNPs (rs1800629 and rs1799964) located at the TNFA gene were genotyped by OpenArray platform in 840 subjects with established cardiovascular disease. Relative telomere length was determined by real time PCR and plasma levels of C-reactive protein by ELISA. In a subgroup of 90 subjects, the gene expression profiles of TNFA, IKKß, p47phox, p40phox, p22phox and gp91phox were determined by qRT-PCR. RESULTS: GG subjects for the SNP rs1800629 at the TNFA gene showed shorter relative telomere length and higher plasma levels of hs-CRP than A-allele subjects (p<0.05). Consistent with these findings, the expression of pro-inflammatory (TNFA) and pro-oxidant (p47phox and the gp91phox) genes was higher in GG subjects than A allele subjects (p<0.05). CONCLUSION: Subjects carrying the GG genotype for the SNP rs1800629 at the TNFA gene show a greater activation of the proinflammatory status than A-allele carriers, which is related to ROS formation. These ROS could induce DNA damage especially in the telomeric sequence, by decreasing the telomere length and inducing cellular aging. This effect may also increase the risk of the development of age-related diseases.

CORonary Diet Intervention with Olive oil and cardiovascular PREVention study (the CORDIOPREV study): Rationale, methods, and baseline characteristics: A clinical trial comparing the efficacy of a Mediterranean diet rich in olive oil versus a low-fat diet on cardiovascular disease in coronary patients.

Coronary heart disease (CHD) represents a major global health burden. However, despite the well-known influence that dietary habits exert over the progression of this disease, there are no well-established and scientifically sound dietary approaches to prevent the onset of clinical outcomes in secondary prevention. The objective of the CORonary Diet Intervention with Olive oil and cardiovascular PREVention study (CORDIOPREV study, clinical trials number NCT00924937) is to compare the ability of a Mediterranean diet rich in virgin olive oil versus a low-fat diet to influence the composite incidence of cardiovascular events after 7 years in subjects with documented CHD at baseline. For this purpose, we enrolled 1,002 coronary patients from Spain. Baseline assessment (2009-2012) included detailed interviews and measurements to assess dietary, social, and biological variables. Results of baseline characteristics: The CORDIOPREV study in Spain describes a population with a high body mass index (37.2% overweight and 56.3% obesity) and with a median of low-density lipoprotein cholesterol of 88.5 mg/dL (70.6% of the patients having <100 mg/dL and 20.3% patients <70 mg/dL). A total of 9.6% of the participants were active smokers, and 64.4% were former smokers. Metabolic syndrome was present in 58% of this population. To sum up, we describe here the rationale, methods, and baseline characteristics of the CORDIOPREV study, which will test for the first time the efficacy of a Mediterranean diet rich in extra virgin olive oil as compared with a low-fat diet on the incidence of CHD recurrence in a long-term follow-up study.

Correction: Influence of Obesity and Metabolic Disease on Carotid Atherosclerosis in Patients with Coronary Artery Disease (CordioPrev Study).

[This corrects the article DOI: 10.1371/journal.pone.0153096.].

Influence of Obesity and Metabolic Disease on Carotid Atherosclerosis in Patients with Coronary Artery Disease (CordioPrev Study).

BACKGROUND: Recent data suggest that the presence of associated metabolic abnormalities may be important modifiers of the association of obesity with a poorer prognosis in coronary heart disease. We determined the influence of isolated overweight and obesity on carotid intima media thickness (IMT-CC), and also assessed whether this influence was determined by the presence of metabolic abnormalities. METHODS: 1002 participants from the CordioPrev study were studied at entry. We determined their metabolic phenotypes and performed carotid ultrasound assessment. We evaluated the influence of obesity, overweight and metabolic phenotypes on the IMT-CC. RESULTS: Metabolically sick participants (defined by the presence of two or more metabolic abnormalities) showed a greater IMT-CC than metabolically healthy individuals (p = 4 * 10(-6)). Overweight and normal weight patients who were metabolically healthy showed a lower IMT-CC than the metabolically abnormal groups (all p<0.05). When we evaluated only body weight (without considering metabolic phenotypes), overweight or obese patients did not differ significantly from normal-weight patients in their IMT-CC (p = 0.077). However, obesity was a determinant of IMT-CC when compared to the composite group of normal weight and overweight patients (all not obese). CONCLUSIONS: In coronary patients, a metabolically abnormal phenotype is associated with a greater IMT-CC, and may be linked to a higher risk of suffering new cardiovascular events. The protection conferred in the IMT-CC by the absence of metabolic abnormality may be blunted by the presence of obesity. TRIAL REGISTRATION: ClinicalTrials.gov NCT00924937.

Statins do not increase the risk of developing type 2 diabetes in familial hypercholesterolemia: The SAFEHEART study.

BACKGROUND: Familial Hypercholesterolemia (FH) is the most common monogenic disorder that causes premature coronary artery disease (CAD). Our objective was to examine the risk of new onset type 2 diabetes mellitus (T2DM) among FH patients and unaffected relatives in relation to treatment with different statins in the SAFEHEART cohort study. METHODS: This is a cross-sectional and prospective cohort study in 2558 FH and 1265 unaffected relatives with a mean follow-up of 5.9 years. Several pertinent data, such as age, gender, metabolic syndrome, lipid profile, body mass index (BMI), waist circumference, HOMA-IR, dose, duration and type of statins, were obtained and examined as predictors of incident diabetes. RESULTS: The new onset diabetes was 1.7% in FH and 0.2% in non FH patients (p=0.001). In multivariate logistic regression, age (OR 1.02, CI 95%: 1.02-1.08), HOMA-IR (OR 1.17, CI 95%: 1.03-1.33), metabolic syndrome (OR 3.3, CI 95%: 1.32-8.28) and specifically plasma glucose, as a component of metabolic syndrome (OR 15.7, CI 95%: 4.70-52.53) were significant predictors of new onset T2DM in the FH group alone. In the adjusted Cox regression model in FH group, age (HR 1.03, CI 95% 1.00-1.06, p=0.031) and metabolic syndrome (HR 4.16, CI 95% 1.58-10.92, p=0.004) remained significant predictors of new onset T2DM. CONCLUSIONS: Our data do not support the postulated diabetogenic effect associated with high-dose statins use in our cohort of FH patients.

Metabolic phenotypes of obesity influence triglyceride and inflammation homoeostasis.

BACKGROUND: We examined the degree of postprandial triglyceride (TG) response over the day, representing a highly dynamic state, with continuous metabolic adaptations, among normal-weight, overweight and obese patients, according to their metabolically healthy or abnormal status. MATERIALS AND METHODS: A total of 1002 patients from the CORDIOPREV clinical trial (NCT00924937) were submitted to an oral fat load test meal with 0·7 g fat/kg body weight (12% saturated fatty acids (SFA), 10% polyunsaturated fatty acids (PUFA), 43% monounsaturated fatty acids (MUFA), 10% protein and 25% carbohydrates). Serial blood test analysing lipid fractions and inflammation markers (high-sensitivity C-reactive protein (hs-CRP)) were drawn at 0, 1, 2, 3 and 4 h during postprandial state. We explored the dynamic response according to six body size phenotypes: (i) normal weight, metabolically healthy; (ii) normal weight, metabolically abnormal; (iii) overweight, metabolically healthy; (iv) overweight, metabolically abnormal; (v) obese, metabolically healthy; and (vi) obese, metabolically abnormal. RESULTS: Metabolically healthy patients displayed lower postprandial response of plasma TG and large triacylglycerol-rich lipoproteins (TRLs)-TG, compared with those metabolically abnormal, independently whether or not they were obese (P < 0·001 and P < 0·001, respectively). Moreover, the area under the curve (AUC) of TG and AUC of large TRLs-TG were greater in the group of metabolically abnormal compared with the group of metabolically healthy (P < 0·001 and P < 0·001, respectively). Interestingly, metabolically abnormal subjects displayed higher postprandial response of plasma hs-CRP than did the subgroup of normal, overweight and obese, metabolically healthy patients (P < 0·001). CONCLUSIONS: Our findings showed that certain types of the metabolic phenotypes of obesity are more favourable modulating phenotypic flexibility after a dynamic fat load test, through TG metabolism and inflammation homoeostasis. To identify, these phenotypes may be the best strategy for personalized treatment of obesity.