BACKGROUND Heart failure (HF) is the fastest growing form of cardiovascular disease both nationally and globally, underlining a need to phenotype subclinical HF intermediaries to improve primary prevention. OBJECTIVES We aimed to identify novel metabolite associations with left ventricular (LV) remodeling, one upstream HF intermediary, among a community-based cohort of individuals. METHODS We examined 1052 Bogalusa Heart Study participants (34.98% African American, 57.41% female, aged 33.6-57.5 years). Measures of LV mass and relative wall thickness (RWT) were obtained using two-dimensional-guided echocardiographic measurements via validated eqs. LV mass was indexed to height2.7 to calculate left ventricular mass index (LVMI). Untargeted metabolomic analysis of fasting serum samples was conducted. In combined and ethnicity-stratified analyses, multivariable linear and multinomial logistic regression models tested the associations of metabolites with the continuous LVMI and RWT and categorical LV geometry phenotypes, respectively, after adjusting for demographic and traditional cardiovascular disease risk factors. RESULTS Pseudouridine (B = 1.38; p = 3.20 × 10-5) and N-formylmethionine (B = 1.65; 3.30 × 10-6) were significantly associated with LVMI in the overall sample as well significant in Caucasians, with consistent effect direction and nominal significance (p < .05) in African Americans. Upon exclusion of individuals with self-report myocardial infarction or congestive HF, we similarly observed a 1.33 g/m2.7 and 1.52 g/m2.7 higher LVMI for each standard deviation increase in pseudouridine and N-formylmethionine, respectively. No significant associations were observed for metabolites with RWT or categorical LV remodeling outcomes. CONCLUSIONS The current analysis identified novel associations of pseudouridine and N-formylmethionine with LVMI, suggesting that mitochondrial-derived metabolites may serve as early biomarkers for LV remodeling and subclinical HF.

中文翻译：

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假尿苷和 N-甲酰甲硫氨酸与左心室质量指数相关：心脏重塑的全代谢组关联分析。

背景 心力衰竭 (HF) 是全国和全球发展最快的心血管疾病形式，强调需要对亚临床 HF 中间体进行表型分析以改善一级预防。目标 我们旨在确定新的代谢物与左心室 (LV) 重塑（一种上游 HF 中介）在社区人群中的关联。方法 我们检查了 1052 名 Bogalusa 心脏研究参与者（34.98% 非裔美国人，57.41% 女性，年龄 33.6-57.5 岁）。LV 质量和相对壁厚 (RWT) 的测量值是通过验证的 eqs 使用二维引导超声心动图测量获得的。LV 质量被索引到 height2.7 以计算左心室质量指数 (LVMI)。对空腹血清样本进行了非靶向代谢组学分析。在综合和种族分层分析中，在调整人口统计学和传统心血管疾病风险因素后，多变量线性和多项逻辑回归模型分别测试了代谢物与连续 LVMI 和 RWT 以及分类 LV 几何表型的关联。结果 假尿苷 (B = 1.38; p = 3.20 × 10-5) 和 N-甲酰甲硫氨酸 (B = 1.65; 3.30 × 10-6) 在整个样本中与 LVMI 显着相关，在高加索人中也显着相关，具有一致的影响方向和非裔美国人的名义显着性 (p < .05)。在排除自我报告的心肌梗死或充血性 HF 的个体后，我们同样观察到假尿苷和 N-甲酰甲硫氨酸的每个标准偏差增加分别增加 1.33 g/m2.7 和 1.52 g/m2.7 的 LVMI。没有观察到代谢物与 RWT 或分类 LV 重塑结果的显着关联。结论 目前的分析确定了假尿苷和 N-甲酰甲硫氨酸与 LVMI 的新关联，表明线粒体衍生代谢物可作为 LV 重塑和亚临床 HF 的早期生物标志物。