Lipid Profiles and Heart Failure Risk: Results From Two Prospective Studies.
Lipid Profiles and Heart Failure Risk: Results From Two Prospective Studies.
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血脂谱和心力衰竭风险：两项前瞻性研究的结果。
DOI：
10.1161/circresaha.120.317883
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发表时间：
2021-02-05
影响因子：
20.1
通讯作者：
Hu FB
中科院分区：
文献类型：
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作者：
Wittenbecher C;Eichelmann F;Toledo E;Guasch-Ferré M;Ruiz-Canela M;Li J;Arós F;Lee CH;Liang L;Salas-Salvadó J;Clish CB;Schulze MB;Martínez-González MÁ;Hu FB
脂质代谢改变与心力衰竭（HF）的发生有关，但尚无前瞻性研究对全面的脂质组学数据和随后的HF风险进行检查。我们的目的是将单一脂质代谢物和脂质组学网络与发生心力衰竭的风险联系起来。发现分析基于病例对照研究中的216种靶向脂质（331例新发HF病例和507例对照，按年龄、性别和研究中心匹配），嵌套在PREDIMED研究中。在条件Logistic回归模型中检查了单一脂质的相关性。此外，脂质组学网络在多步骤工作流程中与HF风险相关联，包括基于机器学习的HF相关网络簇的识别，以及基于回归的这些簇内HF相关脂质模式的发现。如果可用，在EPIC-Potsdam队列的子样本（2414例高危受试者，包括87例新发HF病例）中对重要结果进行外部验证。在混杂因素校正后，两个队列中两种脂质与HF风险显著相关：神经酰胺16：0（PREDIMED中HR/SD为1.28，95%CI 1.13，1.47）和磷脂酰胆碱32_0（PREDIMED中HR/SD为1.23，95%CI 1.08，1.41）。此外，在PREDIMED中，几个网络簇中的脂质模式与HF风险相关。根据标准风险因素进行调整后，基于PREDIMED网络分析中确定的显著HF相关脂质的内部交叉验证评分与较高的HF风险相关（20种脂质，HR/SD 2.33，95%CI 1.93，2.81%）。此外，仅限于外部可用脂质的脂质评分与两个队列中的HF发生率显著相关（PREDIMED中6种脂质，HR/SD为1.30，95%CI 1.14，1.47，EPIC-Potsdam中为1.46，95%CI 1.17，1.82）。我们的研究确定并验证了两种脂质代谢物和几种脂质组学模式作为HF风险的潜在新型生物标志物。血脂谱可以捕获易患HF的临床前分子改变。
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. We aimed to link single lipid metabolites and lipidomics networks to the risk of developing heart failure. 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 study. Associations of single lipids were examined in conditional logistic regression models. Furthermore, lipidomics networks were linked to HF risk in a multi-step 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, two lipids were significantly associated with HF risk in both cohorts: ceramide 16:0 (HR per SD in PREDIMED 1.28, 95%CI 1.13, 1.47) and phosphatidylcholine 32_0 (HR 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, HR 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, HRs per SD 1.30, 95%CI 1.14, 1.47 in PREDIMED, and 1.46, 95%CI, 1.17, 1.82 in EPIC-Potsdam). Our study identified and validated two 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.
影响因子：
7.7
作者：
Iqbal K;Dietrich S;Wittenbecher C;Krumsiek J;Kühn T;Lacruz ME;Kluttig A;Prehn C;Adamski J;von Bergen M;Kaaks R;Schulze MB;Boeing H;Floegel A
通讯作者：
Floegel A