Heart failure Metabolomics: NMR studies

心力衰竭代谢组学：NMR 研究

• 批准号: 10699753
• 负责人: Veronique Roger
• 金额: $ 36.8万
• 依托单位: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10699753
• 关键词: Address; Adrenergic beta-Antagonists; Age; Alanine; Algorithms; American; Angiotensin Receptor; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Body mass index; Books; Branched-Chain Amino Acids; Cardiovascular Diseases; Cessation of life; Characteristics; Chronic; Chronic Obstructive Pulmonary Disease; Citrates; Clinic; Clinical; Clinical Data; Cohort Studies; Communities; Community Health; Complex; Congestive Heart Failure; Creatinine; Data; Diabetes Mellitus; Diagnosis; EFRAC; Electronic Health Record; Enrollment; Epidemiology; Equipment and supply inventories; Evaluation; Glucose; Guidelines; Heart; Heart failure; High Density Lipoproteins; Individual; Insulin Resistance; Investigation; Isoleucine; Ketone Bodies; Leucine; Lipoproteins; Malnutrition; Measurement; Measures; Meta-Analysis; Metabolic; Methods; Mission; New York; Nuclear Magnetic Resonance; Obesity; Optimum Populations; Patients; Persons; Phenotype; Plasma; Population Study; Preventive; Research; Risk; Risk Estimate; Sampling; Smoking; Smoking Status; Societies; Stratification; Survival Rate; Syndrome; Testing; Therapeutic; Triglycerides; Valine; Woman; Work; biobank; clinical risk; cohort; design; epidemiology study; hazard; high risk; indexing; meetings; metabolomics; mortality; mortality risk; novel; particle; prognostic; prognostic value; prospective; risk prediction; sex; systemic inflammatory response; unsupervised learning

Metabolomic signatures This study illustrates a hypothesis generating (discovery) approach to study metabolomics in HF. We performed NMR LipoProfile analysis with the Vantera Clinical Analyzer on plasma samples from our HF community cohort. We measured 25 metabolites (large, medium and small subfractions of triglyceride-rich lipoprotein particles, low- and high-density lipoprotein particles, ketone bodies, branched-chain amino acids, alanine, glucose, citrate, and GlycA). Unsupervised machine learning was used to identify metabolomic clusters from NMR data and their association with mortality was evaluated after stratification for the Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) risk score. We studied 1382 community-dwelling patients with HF median age 78 years (IQR 68- 85); 48.3% women. Unsupervised machine learning identified 2 metabolomic clusters driven by all 25 NMR variables. Survival was 48.2% (95% CI 45.6%-50.9%) at 5 years and differed by cluster assignment 5-year survival rate 61.0% (low-risk cluster) vs. 36.1% (high-risk cluster). Prognostic value of MVX The novel NMR Metabolic Vulnerability Index (MVX; range 1-100) is calculated using indicators of systemic inflammation (small HDL particles, GlycA) and metabolic malnutrition (leucine, valine, isoleucine, citrate). Its prognostic value has not been studied in HF. We tested the hypothesis that MVX was associated with mortality in a HF community cohort. MVX scores in plasma were calculated from NMR LipoProfile analyses conducted on the Vantera NMR analyzer platform using the LP4 deconvolution algorithm. Kaplan-Meier method estimated survival. Proportional hazard regression examined the relationship between MVX quartiles (Q) and mortality, adjusted for Meta-Analysis Global Group in Chronic HF (MAGGIC) score, a validated clinical risk score including ejection fraction, systolic blood pressure, BMI, creatinine, New York Heart Association class, sex, smoking status, diabetes, chronic obstructive pulmonary disease, HF diagnosis >18 months ago, beta blocker, angiotensin converting enzyme inhibitors and angiotensin-receptor blockers. :We studied the population-based cohort of 1,382 patients prospectively enrolled between 2003 and 2012 median age 78 years (IQR 68-85); 48.3% women. Median MVX score was 59.50 (IQR16.55). Higher MVX was associated with lower survival (figure). There was a graded positive association between MVX and death independently of MAGGIC score: (Q2 HR: 1.58, 95% CI 1.33-1.87; Q3 HR: 1.90, 95% CI 1.61-2.25; Q4 HR: 2.30, 95% CI 1.95-2.72). Conclusion: In this cohort, the MVX score was significantly associated with mortality in HF, independently of MAGGIC score, suggesting that measures of metabolic vulnerability may contribute to risk prediction in HF Lipoprotein Insulin Resistance Index (LPIR) sub-study LPIR is a score (0-100; higher values signify greater IR) calculated from 6 lipoprotein subclass/size parameters measured by nuclear magnetic resonance (NMR). We examined the association between LPIR and death in the HF community cohort. LPIR was measured by NMR LipoProfile. MetaAnalysis Global Group in Chronic HF (MAGGIC) scores were calculated from clinical data. Kaplan-Meier curves were used to evaluate survival; Cox regression was used to estimate risk of death by LPIR quartile. Among 1,381 community-dwelling persons with HF, the median LPIR score was 38 (IQR 21-56). Higher LPIR was associated with younger age, diabetes, smoking, obesity, and lower MAGGIC scores, but not ejection fraction. Survival increased by LPIR quartile (p<0.001) and at 5 years was 36% 95% CI 31-42, 42% 95% CI 38-48, 51% 95% CI 46-56, and 65% 95% CI 60-70 for quartile 1-4, respectively. The association between LPIR and death was independent of MAGGIC score. In summary, taken collectively these results indicate that metabolomics provide important information on the characterization of the HF syndrome and adds prognostic value over clinically (guideline recommended) scores. Two abstracts have been presented at the Annual Meeting of the Society for Epidemiology Research in June 2022 (2022-Abstract-Book.pdf (epiresearch.org)) NMR Metabolomics Signatures in Heart Failure: a population-based study Anna Wolska, Jungnam Joo, Alan T. Remaley , James D. Otvos , Maureen Sampson Suzette J. Bielinski , Nicholas B. Larson , Hoyoung Park , Katie Conners , Sarah Turecamo , Veronique L. Roger Metabolic Vulnerability Index and Mortality in Heart Failure: a Community Cohort Study Katie Conners , Hoyoung Park , Jungnam Joo , Sheila M. Manemann , Alan T. Remaley , James D. Otvos , Maureen Sampson , Suzette J Bielinski , Anna Wolska , Sarah Turecamo , Veronique L. Roger One abstract was presented at the Annual Meeting of the American Diabetes Association Lipoprotein Insulin Resistance Index and Mortality in Heart Failure: A Population Study: Sarah Turecamo, Anna Wolska, James D. Otvos, Alan T. Remaley, Katie Conners, Jungnam Joo, Hoyoung Park, Maureen Sampson , Suzette J Bielinski, Veronique L. Roger

代谢组学特征 这项研究说明了一个假设生成（发现）的方法来研究代谢组学在HF。我们使用Vantera临床分析仪对HF社区队列的血浆样本进行了NMR LipoProfile分析。我们测量了25种代谢产物（富含磷脂酰肌醇的脂蛋白颗粒的大、中、小亚组分、低密度和高密度脂蛋白颗粒、酮体、支链氨基酸、丙氨酸、葡萄糖、柠檬酸盐和GlycA）。使用无监督机器学习从NMR数据中识别代谢组学簇，并在慢性心力衰竭荟萃分析全球组（MAGGIC）风险评分分层后评估其与死亡率的相关性。 我们研究了1382名社区居住的HF患者，中位年龄78岁（IQR 68- 85）; 48.3%为女性。无监督机器学习识别了由所有25个NMR变量驱动的2个代谢组学簇。5年生存率为48.2%（95% CI 45.6%-50.9%），不同分组的5年生存率不同，低风险组为61.0%，高风险组为36.1%。 MVX的预后价值 新的NMR代谢脆弱性指数（MVX;范围1-100）是使用全身炎症（小HDL颗粒，GlycA）和代谢性营养不良（亮氨酸，缬氨酸，异亮氨酸，柠檬酸盐）的指标计算的。其预后价值尚未在HF中进行研究。我们在HF社区队列中检验了MVX与死亡率相关的假设。 使用LP 4去卷积算法，根据在Vantera NMR分析仪平台上进行的NMR LipoProfile分析计算血浆中的MVX评分。Kaplan-Meier法估计生存期。比例风险回归检查了MVX四分位数（Q）与死亡率之间的关系，并根据慢性HF荟萃分析全球小组（MAGIC）评分进行了调整，该评分是一种经过验证的临床风险评分，包括射血分数、收缩压、BMI、肌酸酐、纽约心脏协会分级、性别、吸烟状况、糖尿病、慢性阻塞性肺病、心力衰竭诊断>18个月前、β受体阻滞剂、血管紧张素转化酶抑制剂和血管紧张素受体阻断剂。 我们研究了2003年至2012年前瞻性入组的1，382例患者的人群队列，中位年龄为78岁（IQR 68-85）; 48.3%为女性。中位MVX评分为59.50（IQR16.55）。较高的MVX与较低的生存率相关（图）。MVX与死亡之间存在分级正相关性，与MAGGIC评分无关：（Q2 HR：1.58，95% CI 1.33-1.87; Q3 HR：1.90，95% CI 1.61-2.25; Q4 HR：2.30，95% CI 1.95-2.72）。结论：在该队列中，MVX评分与HF死亡率显著相关，独立于MAGGIC评分，提示代谢脆弱性的测量可能有助于HF风险预测 脂蛋白胰岛素抵抗指数（LPIR）子研究 LPIR是从通过核磁共振（NMR）测量的6个脂蛋白亚类/大小参数计算的评分（0-100;值越高表示IR越大）。我们在HF社区队列中研究了LPIR和死亡之间的关系。 通过NMR LipoProfile测量LPIR。荟萃分析慢性HF全球组（MAGGIC）评分根据临床数据计算。Kaplan-Meier曲线用于评估生存率;考克斯回归用于通过LPIR四分位数估计死亡风险。 在1,381名社区居民HF患者中，LPIR评分中位数为38（IQR 21-56）。较高的LPIR与年轻、糖尿病、吸烟、肥胖和较低的MAGGIC评分相关，但与射血分数无关。生存率随LPIR四分位数增加（p<0.001），第1-4四分位数的5年生存率分别为36% 95% CI 31-42、42% 95% CI 38-48、51% 95% CI 46-56和65% 95% CI 60-70。LPIR和死亡之间的关联与MAGGIC评分无关。 总之，这些结果表明，代谢组学提供了HF综合征表征的重要信息，并增加了临床（指南推荐）评分的预后价值。 两篇摘要已在2022年6月的流行病学研究学会年会上发表（2022-Abstract-Book.pdf（epiresearch.org）） 心力衰竭的NMR代谢组学特征：一项基于人群的研究安娜沃尔斯卡，Jungnam Joo，Alan T.作者：James D.放大图片作者：John B.放大图片作者：Larson，Hoyoung Park，Katie Conners，Sarah Turecamo，Veronique L.罗杰 代谢脆弱性指数与心力衰竭死亡率：一项社区队列研究。作者：Alan T.作者：James D.放大图片创作者：Maureen Sampson，Suzette J Bielinski，安娜Wolska，Sarah Turecamo，Veronique L.罗杰 一份摘要在美国糖尿病协会年会上发表 脂蛋白胰岛素抵抗指数与心力衰竭死亡率：一项人群研究：Sarah Turecamo，安娜Wolska，James D.艾伦·奥特沃斯作者：Katie Conners，Jungnam Joo，Hoyoung Park，Maureen Sampson，Suzette J Bielinski，Veronique L.罗杰