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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.