IMPORTANCE: Breast cancer is the leading cause of female cancer burden, and its incidence has increased by more than 20% worldwide since 2008. Some observational studies have suggested that the ...Mediterranean diet may reduce the risk of breast cancer. OBJECTIVE: To evaluate the effect of 2 interventions with Mediterranean diet vs the advice to follow a low-fat diet (control) on breast cancer incidence. DESIGN, SETTING, AND PARTICIPANTS: The PREDIMED study is a 1:1:1 randomized, single-blind, controlled field trial conducted at primary health care centers in Spain. From 2003 to 2009, 4282 women aged 60 to 80 years and at high cardiovascular disease risk were recruited after invitation by their primary care physicians. INTERVENTIONS: Participants were randomly allocated to a Mediterranean diet supplemented with extra-virgin olive oil, a Mediterranean diet supplemented with mixed nuts, or a control diet (advice to reduce dietary fat). MAIN OUTCOMES AND MEASURES: Breast cancer incidence was a prespecified secondary outcome of the trial for women without a prior history of breast cancer (n = 4152). RESULTS: After a median follow-up of 4.8 years, we identified 35 confirmed incident cases of breast cancer. Observed rates (per 1000 person-years) were 1.1 for the Mediterranean diet with extra-virgin olive oil group, 1.8 for the Mediterranean diet with nuts group, and 2.9 for the control group. The multivariable-adjusted hazard ratios vs the control group were 0.31 (95% CI, 0.13-0.77) for the Mediterranean diet with extra-virgin olive oil group and 0.53 (95% CI, 0.23-1.26) for the Mediterranean diet with nuts group. In analyses with yearly cumulative updated dietary exposures, the hazard ratio for each additional 5% of calories from extra-virgin olive oil was 0.72 (95% CI, 0.57-0.90). CONCLUSIONS AND RELEVANCE: This is the first randomized trial finding an effect of a long-term dietary intervention on breast cancer incidence. Our results suggest a beneficial effect of a Mediterranean diet supplemented with extra-virgin olive oil in the primary prevention of breast cancer. These results come from a secondary analysis of a previous trial and are based on few incident cases and, therefore, need to be confirmed in longer-term and larger studies. TRIAL REGISTRATION: ISRCTN.org Identifier: ISRCTN35739639
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.
To determine which lipoprotein properties are associated with greater cardiovascular risk scores and each cardiovascular risk factor.
In two cross-sectional baseline samples of PREDIMED trial volunteers, we assessed the associations of HDL functionality (N = 296) and LDL atherogenicity traits (N = 210) with: 1) the 10-year predicted coronary risk (according to the Framingham-REGICOR score), and 2) classical cardiovascular risk factors.
Greater cardiovascular risk scores were associated with low cholesterol efflux values; oxidized, triglyceride-rich, small HDL particles; and small LDLs with low resistance against oxidation (P-trend<0.05, all). After adjusting for the rest of risk factors; 1) type-2 diabetic individuals presented smaller and more oxidized LDLs (P<0.026, all); 2) dyslipidemic participants had smaller HDLs with an impaired capacity to metabolize cholesterol (P<0.035, all); 3) high body mass index values were associated to lower HDL and LDL size and a lower HDL capacity to esterify cholesterol (P<0.037, all); 4) men presented a greater HDL oxidation and lower HDL vasodilatory capacity (P<0.046, all); and 5) greater ages were related to small, oxidized, cytotoxic LDL particles (P<0.037, all).
Dysfunctional HDL and atherogenic LDL particles are present in high cardiovascular risk patients. Dyslipidemia and male sex are predominantly linked to HDL dysfunctionality, whilst diabetes and advanced age are associated with LDL atherogenicity.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
BACKGROUND: Moderate alcohol consumption is cardioprotective. The mechanism for this beneficial effect might be reduced inflammatory responses, as suggested by prospective studies and small clinical ...trials in men. No studies have evaluated the antiinflammatory effects of wine in women. OBJECTIVE: We investigated whether low-dose intake of white and red wines has differential effects on inflammatory markers in women. DESIGN: In a crossover study, we randomly assigned 35 healthy women to two 4-wk periods of 20 g ethanol/d as white or red wine, preceded by two 4-wk washout periods. Before and after interventions, we measured serum lipids, circulating inflammatory biomarkers, cellular adhesion molecules (CAMs), and adhesion of monocytes to stimulated endothelial cells. RESULTS: HDL cholesterol increased, and the serum concentrations of high-sensitivity C-reactive protein, intercellular adhesion molecule-1, CD40L, and interleukin-6 decreased after either wine (P < 0.01, all). Vascular CAM-1 and E-selectin decreased (P < 0.01) only after red wine. CAM expression by mononuclear cells was blunted after either wine, with a greater suppressant effect of red wine. Enhanced adhesion of monocytes to stimulated endothelial cells was reduced by 51% (95% CI: -57%, -45%) after white wine and by 89% (95% CI: -96%, -82%) after red wine (P = 0.01 for between-wine differences). CONCLUSIONS: Moderate wine consumption is associated with beneficial effects on various inflammatory pathways related to endothelial activation in women. Probably because of its higher polyphenol content, red wine shows superior antiinflammatory effects than does white wine. Reducing low-grade inflammation and endothelial activation may be another potential mechanism by which alcoholic beverages exert their cardioprotective effect.
DNA methylation could be reversible and mouldable by environmental factors, such as dietary exposures. The objective was to analyse whether an intervention with two Mediterranean diets, one rich in ...extra-virgin olive oil (MedDiet + EVOO) and the other one in nuts (MedDiet + nuts), was influencing the methylation status of peripheral white blood cells (PWBCs) genes. A subset of 36 representative individuals were selected within the PREvención con DIeta MEDiterránea (PREDIMED-Navarra) trial, with three intervention groups in high cardiovascular risk volunteers: MedDiet + EVOO, MedDiet + nuts, and a low-fat control group. Methylation was assessed at baseline and at five-year follow-up. Ingenuity pathway analysis showed routes with differentially methylated CpG sites (CpGs) related to intermediate metabolism, diabetes, inflammation, and signal transduction. Two CpGs were specifically selected: cg01081346-
/
and cg17071192-
, being associated with intermediate metabolism. Furthermore, cg01081346 was associated with PUFAs intake, showing a role for specific fatty acids on epigenetic modulation. Specific components of MedDiet, particularly nuts and EVOO, were able to induce methylation changes in several PWBCs genes. These changes may have potential benefits in health; especially those changes in genes related to intermediate metabolism, diabetes, inflammation and signal transduction, which may contribute to explain the role of MedDiet and fat quality on health outcomes.
Early diagnosis is important in familial hypercholesterolemia (FH), a highly atherogenic condition, but internationally agreed clinical diagnostic criteria are lacking. Genetic testing for ...low-density lipoprotein (LDL) receptor (LDLR) and apolipoprotein B (APOB) gene defects is the preferable diagnostic method, but the best phenotype indication to proceed with genetic diagnosis has not been established. The aim of this study was to assess the predictive and accuracy values of standard diagnostic criteria for detecting disease-causing mutations in 825 subjects with clinical FH aged ≥14 years from 3 lipid clinics in Spain. All subjects underwent thorough genetic testing for the detection of LDLR and APOB defects using the Lipochip platform. FH-causing mutations were detected in 459 subjects (55.6%). By logistic regression analysis, familial or personal history of tendon xanthoma (TX) and LDL cholesterol were strongly associated with genetic diagnosis (p <0.005, R 2 = 0.41). In subjects without familial or personal histories of TX, the diagnostic criteria for FH of the Make Early Diagnosis to Prevent Early Deaths (MEDPED) project, based on age-specific LDL cholesterol thresholds, showed sensitivity of 72.4%, specificity of 71.1%, and accuracy of 71.6%. LDL cholesterol ≥190 mg/dl in subjects with familial or personal histories of TX and ≥220, ≥225, and ≥235 mg/dl in those without such histories aged <30, 30 to 39, and ≥40 years, respectively, showed sensitivity of 91.1%, specificity of 71.1%, and accuracy of 74.2% for a positive genetic diagnosis. This new set of diagnostic criteria for FH was validated in an independent group of 440 subjects from 6 additional Spanish lipid clinics. In conclusion, TX and age-adjusted LDL cholesterol cut-off values have the highest value for clinical diagnosis and indication of genetic testing in FH.
Metabolic syndrome (MetS) is associated with alterations of lipoprotein structure and function that can be characterized with advanced lipoprotein testing (ADLT). The effect of the Mediterranean diet ...(MedDiet) and weight loss on the lipoprotein subclass profile has been scarcely studied. Within the PREDIMED-Plus randomized controlled trial, a sub-study conducted at Bellvitge Hospital recruiting center evaluated the effects of a weight loss program based on an energy-reduced MedDiet (er-MedDiet) and physical activity (PA) promotion (intervention group) compared with energy-unrestricted MedDiet recommendations (control group) on ADLT-assessed lipoprotein subclasses. 202 patients with MetS (
= 107, intervention;
= 95, control) were included. Lipid profiles were determined, and ADLT was performed at baseline, 6, and 12 months. Linear mixed models were used to assess the effects of intervention on lipoprotein profiles. Compared to the control diet, at 12 months, the er-MedDiet+PA resulted in a significant additional 4.2 kg of body weight loss, a decrease in body mass index by 1.4 kg/m
, reduction in waist circumference by 2.2 cm, decreased triglycerides, LDL-cholesterol and non-HDL-cholesterol, and increased HDL-cholesterol. In er-MedDiet+PA participants, ADLT revealed a decrease in small dense-LDL-cholesterol (sd-LDL-C), intermediate-density lipoproteins, VLDL-triglyceride, and HDL-Triglyceride, and an increase in large LDL and large VLDL particles. In conclusion, compared to an ad libitum MedDiet (control group), er-MedDiet+PA decreased plasma triglycerides and the triglyceride content in HDL and VLDL particles, decreased sd-LDL-C, and increased large LDL particles, indicating beneficial changes against cardiovascular disease.
Walnut consumption is associated with lower risk of type 2 diabetes (T2D) and cardiovascular disease (CVD). However, it is unknown whether plasma metabolites related to walnut consumption are also ...associated with lower risk of cardiometabolic diseases.
The study aimed to identify plasma metabolites associated with walnut consumption and evaluate the prospective associations between the identified profile and risk of T2D and CVD.
The discovery population included 1833 participants at high cardiovascular risk from the PREvención con DIeta MEDiterránea (PREDIMED) study with available metabolomics data at baseline. The study population included 57% women (baseline mean BMI (in kg/m2): 29.9; mean age: 67 y). A total of 1522 participants also had available metabolomics data at year 1 and were used as the internal validation population. Plasma metabolomics analyses were performed using LC-MS. Cross-sectional associations between 385 known metabolites and walnut consumption were assessed using elastic net continuous regression analysis. A 10-cross-validation (CV) procedure was used, and Pearson correlation coefficients were assessed between metabolite weighted models and self-reported walnut consumption in each pair of training–validation data sets within the discovery population. We further estimated the prospective associations between the identified metabolite profile and incident T2D and CVD using multivariable Cox regression models.
A total of 19 metabolites were significantly associated with walnut consumption, including lipids, purines, acylcarnitines, and amino acids. Ten-CV Pearson correlation coefficients between self-reported walnut consumption and the plasma metabolite profile were 0.16 (95% CI: 0.11, 0.20) in the discovery population and 0.15 (95% CI: 0.10, 0.20) in the validation population. The metabolite profile was inversely associated with T2D incidence (HR per 1 SD: 0.83; 95% CI: 0.71, 0.97; P = 0.02). For CVD incidence, the HR per 1-SD was 0.71 (95% CI: 0.60, 0.85; P < 0.001).
A metabolite profile including 19 metabolites was associated with walnut consumption and with a lower risk of incident T2D and CVD in a Mediterranean population at high cardiovascular risk.
Insulin resistance is a complex metabolic disorder and is often associated with type 2 diabetes (T2D).
The aim of this study was to test whether baseline metabolites can additionally improve the ...prediction of insulin resistance beyond classical risk factors. Furthermore, we examined whether a multimetabolite model predicting insulin resistance in nondiabetics can also predict incident T2D.
We used a case-cohort study nested within the Prevención con Dieta Mediterránea (PREDIMED) trial in subsets of 700, 500, and 256 participants without T2D at baseline and 1 and 3 y. Fasting plasma metabolites were semiquantitatively profiled with liquid chromatography–tandem mass spectrometry. We assessed associations between metabolite concentrations and the homeostasis model of insulin resistance (HOMA-IR) through the use of elastic net regression analysis. We subsequently examined associations between the baseline HOMA-IR–related multimetabolite model and T2D incidence through the use of weighted Cox proportional hazard models.
We identified a set of baseline metabolites associated with HOMA-IR. One-year changes in metabolites were also significantly associated with HOMA-IR. The area under the curve was significantly greater for the model containing the classical risk factors and metabolites together compared with classical risk factors alone at baseline 0.81 (95% CI: 0.79, 0.84) compared with 0.69 (95% CI: 0.66, 0.73) and during a 1-y period 0.69 (95% CI: 0.66, 0.72) compared with 0.57 (95% CI: 0.53, 0.62). The variance in HOMA-IR explained by the combination of metabolites and classical risk factors was also higher in all time periods. The estimated HRs for incident T2D in the multimetabolite score (model 3) predicting high HOMA-IR (median value or higher) or HOMA-IR (continuous) at baseline were 2.00 (95% CI: 1.58, 2.55) and 2.24 (95% CI: 1.72, 2.90), respectively, after adjustment for T2D risk factors.
The multimetabolite model identified in our study notably improved the predictive ability for HOMA-IR beyond classical risk factors and significantly predicted the risk of T2D.
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