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Lipid Profiles and Heart Failure Risk: Results From Two Prospective Studies.
Wittenbecher, C, Eichelmann, F, Toledo, E, Guasch-Ferré, M, Ruiz-Canela, M, Li, J, Arós, F, Lee, CH, Liang, L, Salas-Salvadó, J, et al
Circulation research. 2021;(3):309-320
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Abstract
RATIONALE Altered lipid metabolism has been implicated in heart failure (HF) development, but no prospective studies have examined comprehensive lipidomics data and subsequent risk of HF. OBJECTIVE We aimed to link single lipid metabolites and lipidomics networks to the risk of developing HF. METHODS AND RESULTS Discovery analyses were based on 216 targeted lipids in a case-control study (331 incident HF cases and 507 controls, matched by age, sex, and study center), nested within the PREDIMED (Prevención con Dieta Mediterránea) study. Associations of single lipids were examined in conditional logistic regression models. Furthermore, lipidomics networks were linked to HF risk in a multistep workflow, including machine learning-based identification of the HF-related network clusters, and regression-based discovery of the HF-related lipid patterns within these clusters. If available, significant findings were externally validated in a subsample of the EPIC-Potsdam cohort (2414 at-risk participants, including 87 incident HF cases). After confounder-adjustments, 2 lipids were significantly associated with HF risk in both cohorts: CER (ceramide) 16:0 (relative risk [RR] per SD in PREDIMED, 1.28 [95% CI, 1.13-1.47]) and phosphatidylcholine 32_0 (RR per SD in PREDIMED, 1.23 [95% CI, 1.08-1.41]). Additionally, lipid patterns in several network clusters were associated with HF risk in PREDIMED. Adjusted for standard risk factors, an internally cross-validated score based on the significant HF-related lipids that were identified in the network analysis in PREDIMED was associated with a higher HF risk (20 lipids, RR per SD, 2.33 [95% CI, 1.93%-2.81%). Moreover, a lipid score restricted to the externally available lipids was significantly associated with HF incidence in both cohorts (6 lipids, RRs per SD, 1.30 [95% CI, 1.14-1.47] in PREDIMED, and 1.46 [95% CI, 1.17-1.82] in EPIC-Potsdam). CONCLUSIONS Our study identified and validated 2 lipid metabolites and several lipidomics patterns as potential novel biomarkers of HF risk. Lipid profiling may capture preclinical molecular alterations that predispose for incident HF. Registration: URL: https://www.isrctn.com/ISRCTN35739639; Unique identifier: ISRCTN35739639.
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Changes in Plasma Metabolite Concentrations after a Low-Glycemic Index Diet Intervention.
Hernández-Alonso, P, Giardina, S, Cañueto, D, Salas-Salvadó, J, Cañellas, N, Bulló, M
Molecular nutrition & food research. 2019;(1):e1700975
Abstract
SCOPE To examine whether a low-glycemic index (LGI) diet improves a set of plasma metabolites related to different metabolic diseases, and comparison to a high-glycemic index (HGI) diet and a low-fat (LF) diet. METHODS AND RESULTS A parallel, randomized trial with three intervention diets: an LGI diet, an HGI diet, and an LF diet. A total of 122 adult overweight and obese subjects were enrolled in the study for 6 months. Blood samples were collected at baseline and at the end of the intervention. The plasma metabolomic profile of 102 subjects was analyzed using three different approaches: GC/quadrupole-TOF, LC/quadrupole-TOF, and nuclear magnetic resonance. Both univariate and multivariate analysis were performed. Serine levels were significantly higher following the LGI diet compared to both the HGI and LF diets (q = 0.002), whereas leucine (q = 0.015) and valine (q = 0.024) were lower in the LGI diet compared to the LF diet. A set of two sphingomyelins, two lysophosphatidylcholines, and six phosphatidylcholines were significantly modulated after the LGI diet compared to the HGI and LF diets (q < 0.05). Significant correlations between changes in plasma amino acids and lipid species with changes in body weight, glucose, insulin, and some inflammatory markers are also reported. CONCLUSION These results suggest that an LGI diet modulates certain circulating amino acids and lipid levels. These findings may explain the health benefits attributed to LGI diets in metabolic diseases such as type 2 diabetes.
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Lipid metabolic networks, Mediterranean diet and cardiovascular disease in the PREDIMED trial.
Wang, DD, Zheng, Y, Toledo, E, Razquin, C, Ruiz-Canela, M, Guasch-Ferré, M, Yu, E, Corella, D, Gómez-Gracia, E, Fiol, M, et al
International journal of epidemiology. 2018;(6):1830-1845
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BACKGROUND Perturbed lipid metabolic pathways may play important roles in the development of cardiovascular disease (CVD). However, existing epidemiological studies have focused more on discovering individual lipid metabolites for CVD risk prediction rather than assessing metabolic pathways. METHODS This study included a subcohort of 787 participants and all 230 incident CVD cases from the PREDIMED trial. Applying a network-based analytical method, we identified lipid subnetworks and clusters from a global network of 200 lipid metabolites and linked these subnetworks/clusters to CVD risk. RESULTS Lipid metabolites with more double bonds clustered within one subnetwork, whereas lipid metabolites with fewer double bonds clustered within other subnetworks. We identified 10 lipid clusters that were divergently associated with CVD risk. The hazard ratios [HRs, 95% confidence interval (CI)] of CVD per a 1-standard deviation (SD) increment in cluster score were 1.39 (1.17-1.66) for the hydroxylated phosphatidylcholine (HPC) cluster and 1.24 (1.11-1.37) for a cluster that included diglycerides and a monoglyceride with stearic acyl chain. Every 1-SD increase in the score of cluster that included highly unsaturated phospholipids and cholesterol esters was associated with an HR for CVD of 0.81 (95% CI, 0.67-0.98). Despite a suggestion that MedDiet modified the association between a subnetwork that included most lipids with a high degree of unsaturation and CVD, changes in lipid subnetworks/clusters during the first-year follow-up were not significantly different between intervention groups. CONCLUSIONS The degree of unsaturation was a major determinant of the architecture of lipid metabolic network. Lipid clusters that strongly predicted CVD risk, such as the HPC cluster, warrant further functional investigations.
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Effects of walnut consumption on blood lipids and other cardiovascular risk factors: an updated meta-analysis and systematic review of controlled trials.
Guasch-Ferré, M, Li, J, Hu, FB, Salas-Salvadó, J, Tobias, DK
The American journal of clinical nutrition. 2018;(1):174-187
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Abstract
BACKGROUND Intervention studies suggest that incorporating walnuts into the diet may improve blood lipids without promoting weight gain. OBJECTIVE We conducted a systematic review and meta-analysis of controlled trials evaluating the effects of walnut consumption on blood lipids and other cardiovascular risk factors. DESIGN We conducted a comprehensive search of PubMed and EMBASE databases (from database inception to January 2018) of clinical trials comparing walnut-enriched diets with control diets. We performed random-effects meta-analyses comparing walnut-enriched and control diets for changes in pre-post intervention in blood lipids (mmol/L), apolipoproteins (mg/dL), body weight (kg), and blood pressure (mm Hg). RESULTS Twenty-six clinical trials with a total of 1059 participants were included. The following weighted mean differences (WMDs) in reductions were obtained for walnut-enriched diets compared with control groups: -6.99 mg/dL (95% CI: -9.39, -4.58 mg/dL; P < 0.001) (3.25% greater reduction) for total blood cholesterol (TC) and -5.51 mg/dL (95% CI: -7.72, -3.29 mg/dL; P < 0.001) (3.73% greater reduction) for low-density lipoprotein (LDL) cholesterol. Triglyceride concentrations were also reduced in walnut-enriched diets compared with control [WMD = -4.69 (95% CI: -8.93, -0.45); P = 0.03; 5.52% greater reduction]. More pronounced reductions in blood lipids were observed when walnut interventions were compared with American and Western diets [WMD for TC = -12.30 (95% CI: -23.17, -1.43) and for LDL = -8.28 (95% CI: -13.04, -3.51); P < 0.001]. Apolipoprotein B (mg/dL) was also reduced significantly more on walnut-enriched diets compared with control groups [WMD = -3.74 (95% CI: -6.51, -0.97); P = 0.008] and a trend towards a reduction was observed for apolipoprotein A [WMD = -2.91 (95% CI: -5.98, 0.08); P = 0.057]. Walnut-enriched diets did not lead to significant differences in weight change (kg) compared with control diets [WMD = -0.12 (95% CI: -2.12, 1.88); P = 0.90], systolic blood pressure (mm Hg) [WMD = -0.72 (95% CI: -2.75, 1.30); P = 0.48], or diastolic blood pressure (mm Hg) [WMD = -0.10 (95% CI: -1.49, 1.30); P = 0.88]. CONCLUSIONS Incorporating walnuts into the diet improved blood lipid profile without adversely affecting body weight or blood pressure.
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Mediterranean Diet Improves High-Density Lipoprotein Function in High-Cardiovascular-Risk Individuals: A Randomized Controlled Trial.
Hernáez, Á, Castañer, O, Elosua, R, Pintó, X, Estruch, R, Salas-Salvadó, J, Corella, D, Arós, F, Serra-Majem, L, Fiol, M, et al
Circulation. 2017;(7):633-643
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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 of 2 TMDs, one enriched with virgin olive oil (TMD-VOO; n=100) and the other enriched with nuts (TMD-Nuts; n=100), with respect to a low-fat control diet (n=96). We assessed the effects of both TMDs on the role of HDL particles on reverse cholesterol transport (cholesterol efflux capacity, HDL ability to esterify cholesterol, and cholesteryl ester transfer protein activity), HDL antioxidant properties (paraoxonase-1 arylesterase activity and total HDL antioxidant capacity on low-density lipoproteins), and HDL vasodilatory capacity (HDL ability to induce the release of nitric oxide in endothelial cells). We also studied the effects of a TMD on several HDL quality-related characteristics (HDL particle oxidation, resistance against oxidative modification, main lipid and protein composition, and size distribution). RESULTS Both TMDs increased cholesterol efflux capacity relative to baseline (P=0.018 and P=0.013 for TMD-VOO and TMD-Nuts, respectively). The TMD-VOO intervention decreased cholesteryl ester transfer protein activity (relative to baseline, P=0.028) and increased HDL ability to esterify cholesterol, paraoxonase-1 arylesterase activity, and HDL vasodilatory capacity (relative to control, P=0.039, P=0.012, and P=0.026, respectively). Adherence to a TMD induced these beneficial changes by improving HDL oxidative status and composition. The 3 diets increased the percentage of large HDL particles (relative to baseline, P<0.001). CONCLUSIONS The TMD, especially when enriched with virgin olive oil, improved HDL atheroprotective functions in humans. CLINICAL TRIAL REGISTRATION URL: http://www.controlled-trials.com. Unique identifier: ISRCTN35739639.
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Plasma lipidomic profiles and cardiovascular events in a randomized intervention trial with the Mediterranean diet.
Toledo, E, Wang, DD, Ruiz-Canela, M, Clish, CB, Razquin, C, Zheng, Y, Guasch-Ferré, M, Hruby, A, Corella, D, Gómez-Gracia, E, et al
The American journal of clinical nutrition. 2017;(4):973-983
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Background: Lipid metabolites may partially explain the inverse association between the Mediterranean diet (MedDiet) and cardiovascular disease (CVD).Objective: We evaluated the associations between 1) lipid species and the risk of CVD (myocardial infarction, stroke, or cardiovascular death); 2) a MedDiet intervention [supplemented with extra virgin olive oil (EVOO) or nuts] and 1-y changes in these molecules; and 3) 1-y changes in lipid species and subsequent CVD.Design: With the use of a case-cohort design, we profiled 202 lipid species at baseline and after 1 y of intervention in the PREDIMED (PREvención con DIeta MEDiterránea) trial in 983 participants [230 cases and a random subcohort of 790 participants (37 overlapping cases)].Results: Baseline concentrations of cholesterol esters (CEs) were inversely associated with CVD. A shorter chain length and higher saturation of some lipids were directly associated with CVD. After adjusting for multiple testing, direct associations remained significant for 20 lipids, and inverse associations remained significant for 6 lipids. When lipid species were weighted by the number of carbon atoms and double bonds, the strongest inverse association was found for CEs [HR: 0.39 (95% CI: 0.22, 0.68)] between extreme quintiles (P-trend = 0.002). Participants in the MedDiet + EVOO and MedDiet + nut groups experienced significant (P < 0.05) 1-y changes in 20 and 17 lipids, respectively, compared with the control group. Of these changes, only those in CE(20:3) in the MedDiet + nuts group remained significant after correcting for multiple testing. None of the 1-y changes was significantly associated with CVD risk after correcting for multiple comparisons.Conclusions: Although the MedDiet interventions induced some significant 1-y changes in the lipidome, they were not significantly associated with subsequent CVD risk. Lipid metabolites with a longer acyl chain and higher number of double bonds at baseline were significantly and inversely associated with the risk of CVD.
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Mediterranean diet reduces 24-hour ambulatory blood pressure, blood glucose, and lipids: one-year randomized, clinical trial.
Doménech, M, Roman, P, Lapetra, J, García de la Corte, FJ, Sala-Vila, A, de la Torre, R, Corella, D, Salas-Salvadó, J, Ruiz-Gutiérrez, V, Lamuela-Raventós, RM, et al
Hypertension (Dallas, Tex. : 1979). 2014;(1):69-76
Abstract
UNLABELLED The PREvención con DIeta MEDiterránea (PREDIMED) trial showed that Mediterranean diets (MedDiets) supplemented with either extravirgin olive oil or nuts reduced cardiovascular events, particularly stroke, compared with a control, lower fat diet. The mechanisms of cardiovascular protection remain unclear. We evaluated the 1-year effects of supplemented MedDiets on 24-hour ambulatory blood pressure (BP), blood glucose, and lipids. Randomized, parallel-design, controlled trial was conducted in 2 PREDIMED sites. Diets were ad libitum, and no advice on increasing physical activity or reducing sodium intake was given. Participants were 235 subjects (56.5% women; mean age, 66.5 years) at high cardiovascular risk (85.4% with hypertension). Adjusted changes from baseline in mean systolic BP were -2.3 (95% confidence interval [CI], -4.0 to -0.5) mm Hg and -2.6 (95% CI, -4.3 to -0.9) mm Hg in the MedDiets with olive oil and the MedDiets with nuts, respectively, and 1.7 (95% CI, -0.1 to 3.5) mm Hg in the control group (P<0.001). Respective changes in mean diastolic BP were -1.2 (95% CI, -2.2 to -0.2), -1.2 (95% CI, -2.2 to -0.2), and 0.7 (95% CI, -0.4 to 1.7) mm Hg (P=0.017). Daytime and nighttime BP followed similar patterns. Mean changes from baseline in fasting blood glucose were -6.1, -4.6, and 3.5 mg/dL (P=0.016) in the MedDiets with olive oil, MedDiets with nuts, and control diet, respectively; those of total cholesterol were -11.3, -13.6, and -4.4 mg/dL (P=0.043), respectively. In high-risk individuals, most with treated hypertension, MedDiets supplemented with extravirgin olive oil or nuts reduced 24-hour ambulatory BP, total cholesterol, and fasting glucose. CLINICAL TRIAL REGISTRATION URL http://www.clinicaltrials.gov. Unique identifier: ISRCTN35739639.
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Effects of soluble fiber (Plantago ovata husk) on plasma lipids, lipoproteins, and apolipoproteins in men with ischemic heart disease.
Solà, R, Godàs, G, Ribalta, J, Vallvé, JC, Girona, J, Anguera, A, Ostos, M, Recalde, D, Salazar, J, Caslake, M, et al
The American journal of clinical nutrition. 2007;(4):1157-63
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BACKGROUND New dietary strategies to reduce cardiovascular disease (CVD) risk include the addition of fiber to the diet. The effect of soluble-fiber consumption derived from Plantago ovata husk on lipid risk factors in patients with CVD is unknown. OBJECTIVE We compared the effects of soluble fiber (P. ovata husk) with those of insoluble fiber (P. ovata seeds) on plasma lipid, lipoprotein, and apolipoprotein (apo) concentrations within a CVD secondary prevention program. DESIGN In a randomized, crossover, controlled, single-blind design, 28 men with CVD (myocardial infarction or stable angina) and an LDL-cholesterol concentration ≤3.35 mmol/L consumed for 8 wk, under controlled conditions, a low-saturated-fat diet supplemented with 10.5 g P. ovata husk/d or 10.5 g P. ovata seeds/d. Fasting plasma lipid concentrations and polymorphisms of genes involved in lipid metabolism, such as apo A-IV, apo E, and fatty acid-binding protein, were measured. RESULTS Plasma triacylglycerol decreased (6.7%; P < 0.02), the ratio of apo B 100 to apo A-I decreased (4.7%; P < 0.02), and apo A-I increased (4.3%; P < 0.01) in the P. ovata husk consumers. Compared with the intake of insoluble fiber, the intake of P. ovata husk increased HDL-cholesterol concentrations by 6.7% (P = 0.006) and decreased the ratio of total to HDL cholesterol and of LDL to HDL cholesterol by 10.6% (P = 0.002) and 14.2% (P = 0.003), respectively. CONCLUSION In the secondary prevention of CVD, P. ovata husk intake induces a more beneficial effect on the cardiovascular lipid risk-factor profile than does an equivalent intake of insoluble fiber.
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Conjugated linoleic acid intake in humans: a systematic review focusing on its effect on body composition, glucose, and lipid metabolism.
Salas-Salvadó, J, Márquez-Sandoval, F, Bulló, M
Critical reviews in food science and nutrition. 2006;(6):479-88
Abstract
Studies performed on different species show that the consumption of conjugated linoleic acid (CLA) leads to a loss of fat and total body weight, reduces the plasma concentrations of total and LDL cholesterol, and has an antiinflammatory effect. This article reviews the clinical trials on human beings that evaluate how mixtures of CLA isomers administered as supplements or CLA-enriched products can affect total body weight, body composition, plasma lipid profile, glycemia, insulinemia, insulin sensitivity, lipid oxidation, and inflammation. After analyzing the few studies published to date in reduced samples of healthy humans or patients with overweight, obesity, metabolic syndrome, or diabetes, we deduce that there is not enough evidence to show that conjugated linoleic acid has an effect on weight and body composition in humans. However, some of these studies have observed that the administration of various CLA isomers has adverse effects on lipid profile (it decreases HDL cholesterol concentration and increases Lp(a) circulating levels), glucose metabolism (glycemia, insulinemia or insulin sensitivity), lipid oxidation, inflammation, or endothelial function. Therefore, long-term randomized clinical trials, controlled with placebo, need to be made in large samples of patients to evaluate the efficacy and safety of CLA isomers before its indiscriminate use in human beings can be recommended.