Heart failure Metabolomics: NMR studies

心力衰竭代谢组学：NMR 研究

• 批准号: 10929211
• 负责人: Veronique Roger
• 金额: $ 41.79万
• 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/10929211
• 关键词: Address; Adrenergic beta-Antagonists; Age; Alanine; Algorithms; American; American Heart Association; Angiotensin Receptor; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Body mass index; Books; Branched-Chain Amino Acids; Cardiovascular Diseases; Cessation of life; Characteristics; 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; Life Style; Lipoproteins; Malnutrition; Manuscripts; Measurement; Measures; Meta-Analysis; Metabolic; Methods; Mission; New York; Nuclear Magnetic Resonance; Obesity; Patients; Persons; Phenotype; Plasma; Population; Population Study; Preventive; Publishing; Recommendation; 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; frailty; hazard; high risk; indexing; meetings; metabolomics; mortality; mortality risk; novel; particle; prognostic; prognostic value; prospective; risk prediction; risk stratification; 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 Two abstracts were presented at the 2023 American Heart Association Epidemiology Meeting Circulating ketone bodies and mortality in heart failure: a community cohort study Rebecca Oyetoro, Katie Conners, Jungnam Joo, Sarah Turecamo, Maureen Sampson, Anna Wolska, Alan T. Remaley, Margery Connelly, James D. Otvos, Nicholas B. Larson, Suzette J. Bielinski, Joseph J. Shearer, Veronique L. Roger AHA Epi Lifestyle 2023 Metabolic Vulnerability and Frailty for Risk Stratification in Heart Failure: A Community Cohort study Sant J. Kumar, Katie Conners, Jungnam Joo, Sarah Turecamo, Maureen Sampson, Anna Wolska, Alan T. Remaley, Margery A. Connelly, James D. Otvos, Nicholas B. Larson, Suzette J. Bielinski, Joseph J. Shearer, Veronique L. Roger AHA Epi Lifestyle 2023 In addition to the published manuscript listed below Three manuscripts are under review included two in revision

代谢组学特征