Lipid Profiles and Heart Failure Risk: Results From Two Prospective Studies
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Lipid Profiles and Heart Failure Risk : Results From Two Prospective Studies. / Wittenbecher, Clemens; Eichelmann, Fabian; Toledo, Estefanía; Guasch-Ferré, Marta; Ruiz-Canela, Miguel; Li, Jun; Arós, Fernando; Lee, Chih Hao; Liang, Liming; Salas-Salvadó, Jordi; Clish, Clary B.; Schulze, Matthias B.; Martínez-González, Miguel Ángel; Hu, Frank B.
In: Circulation Research, Vol. 128, No. 3, 2021, p. 309-320.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Lipid Profiles and Heart Failure Risk
T2 - Results From Two Prospective Studies
AU - Wittenbecher, Clemens
AU - Eichelmann, Fabian
AU - Toledo, Estefanía
AU - Guasch-Ferré, Marta
AU - Ruiz-Canela, Miguel
AU - Li, Jun
AU - Arós, Fernando
AU - Lee, Chih Hao
AU - Liang, Liming
AU - Salas-Salvadó, Jordi
AU - Clish, Clary B.
AU - Schulze, Matthias B.
AU - Martínez-González, Miguel Ángel
AU - Hu, Frank B.
N1 - Publisher Copyright: © 2020 American Heart Association, Inc.
PY - 2021
Y1 - 2021
N2 - 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.
AB - 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.
KW - biomarker
KW - heart failure
KW - lipidomics
KW - lipids
KW - metabolism
U2 - 10.1161/CIRCRESAHA.120.317883
DO - 10.1161/CIRCRESAHA.120.317883
M3 - Journal article
C2 - 33272114
AN - SCOPUS:85102018619
VL - 128
SP - 309
EP - 320
JO - Circulation Research
JF - Circulation Research
SN - 0009-7330
IS - 3
ER -
ID: 357885254