Heart failure Metabolomics: NMR studies

代谢组学特征 这项研究说明了一种假说生成(发现)的方法来研究心衰的代谢组学。我们使用Vantera临床分析仪对我们心力衰竭社区队列的血浆样本进行了核磁共振脂谱分析。我们测量了25种代谢物(富含甘油三酯的脂蛋白颗粒的大、中、小亚组分，低密度脂蛋白颗粒和高密度脂蛋白颗粒，酮体，支链氨基酸，丙氨酸，葡萄糖，柠檬酸和甘氨酸)。无监督机器学习被用来从核磁共振数据中识别代谢组，并在Meta-分析慢性心力衰竭全球组(MAGGIC)风险评分分层后评估它们与死亡率的相关性。 我们研究了1382名居住在社区的心力衰竭患者，他们的平均年龄为78岁(IQR68-85)，其中48.3%是女性。无监督机器学习确定了由所有25个核磁共振变量驱动的2个代谢组。5年生存率为48.2%(95%可信区间为45.6%~50.9%)，不同分组的5年生存率分别为61.0%(低风险组)和36.1%(高危组)。 MVX的预后价值 新的核磁共振代谢脆弱性指数(MVX；范围1-100)是使用全身炎症(小高密度脂蛋白颗粒，GlycA)和代谢营养不良(亮氨酸、缬氨酸、异亮氨酸、柠檬酸盐)的指标来计算的。其预后价值在心力衰竭中尚未被研究。我们在心力衰竭社区队列中检验了MVX与死亡率相关的假设。 血浆中的MVX分数是通过在Vantera核磁共振分析仪平台上使用LP4去卷积算法进行的核磁共振脂谱分析来计算的。Kaplan-Meier法估计生存时间。比例风险回归研究了MVX四分位数(Q)与死亡率之间的关系，并根据Meta分析全球慢性心力衰竭小组(MAGGIC)评分进行了调整，MAGGIC评分是一个经过验证的临床风险评分，包括射血分数、收缩压、体重指数、肌酐、纽约心脏协会分级、性别、吸烟状况、糖尿病、慢性阻塞性肺疾病、心力衰竭诊断和治疗；18个月前，β受体阻滞剂、血管紧张素转换酶抑制剂和血管紧张素受体阻滞剂。 ：我们研究了2003至2012年间前瞻性登记的1382名患者的基于人群的队列，年龄中值为78岁(IQR 68-85)；其中48.3%为女性。MVX评分中位数为59.50(IQR16.55)。MVX越高，生存率越低(图)。独立于MAGGIC评分，MVX与死亡率呈正相关：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评分与心力衰竭的死亡率显著相关，独立于MAGGIC评分，提示代谢易损性的测量可能有助于心力衰竭的风险预测。 脂蛋白胰岛素抵抗指数(LPIR)亚研究 LPIR是根据核磁共振测量的6个脂蛋白亚类/大小参数计算得出的分数(0-100；值越高意味着IR越大)。我们在心力衰竭社区队列中研究了LPIR和死亡之间的关系。 用核磁共振脂谱测定LPIR。Metaanalysis Global Group in Chronic HF(MAGGIC)评分根据临床数据计算。生存评估采用Kaplan-Meier曲线，LPIR四分位数采用Cox回归方法估计死亡风险。 在1381名患有心力衰竭的社区居民中，LPIR得分中位数为38(IQR 21-56)。较高的LPIR与较年轻的年龄、糖尿病、吸烟、肥胖和较低的MAGGIC评分有关，但与射血分数无关。LPIR四分位数(p&lt；0.001)提高了患者的生存率，五年后四分位数的生存率分别为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。 综上所述，这些结果表明代谢组学为心力衰竭综合征的特征提供了重要的信息，并比临床(指南推荐的)评分增加了预后价值。 已在2022年6月流行病学研究会年会上提交了两篇摘要(2022-Abstract-Book.pdf(epetreearch.org)) 心力衰竭的核磁共振代谢组学签名：一项基于人群的研究安娜·沃尔斯卡，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 心力衰竭中的代谢易损性指数和死亡率：社区队列研究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 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：人群研究：Sarah Turecamo，Anna Wolska，James D.Otvos，Alan T.Remaley，Katie Conners，Jungnam Joo，HoYoung Park，Maureen Sampson，Suzette J Bielinski，Veronique L.Roger

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