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C-Reactive Protein, Interleukin-6, Trimethylamine-N-Oxide, Syndecan-1, Nitric Oxide, and Tumor Necrosis Factor Receptor-1 in Heart Failure with Preserved Versus Reduced Ejection Fraction: a Meta-Analysis

  • Clinical Heart Failure (T Meyer, Section Editor)
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Abstract

Purpose of Review

The purpose of this review was to synthesize the evidence on non-traditional biomarkers from proteomic and metabolomic studies that may distinguish heart failure (HF) with preserved ejection fraction (HFpEF) from heart failure with reduced ejection fraction (HFrEF) and non-HF.

Recent Findings

Understanding the pathophysiology of HFpEF continues to be challenging. A number of inflammatory and metabolic biomarkers that have recently been suggested to be involved include C-reactive protein (CRP), interleukin-6 (IL-6), trimethylamine-N-oxide (TMAO), syndecan-1 (SDC-1), nitric oxide (NO), and tumor necrosis factor receptor-1 (TNFR-1).

Summary

A systematic search was conducted using Medline, EMBASE, and Web of Science with search terms such as “HFpEF,” “metabolomics,” and “proteomics,” and a meta-analysis was conducted. The results demonstrate significantly higher levels of TMAO, CRP, SDC-1, and IL-6 in HFpEF compared to controls without HF and significantly higher levels of TMAO and CRP in HFrEF compared to controls. The results further suggest that HFpEF might be distinguishable from HFrEF based on higher levels of IL-6 and lower levels of SDC-1 and NO. These data may reflect pathophysiological differences between HFpEF and HFrEF.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Heidenreich PA, Albert NM, Allen LA, Bluemke DA, Butler J, Fonarow GC, et al. Forecasting the impact of heart failure in the United States: a policy statement from the American Heart Association. Circ Heart Fail. 2013;6:606–19. https://doi.org/10.1161/HHF.0b013e318291329a.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Steinberg BA, Zhao X, Heidenreich PA, Peterson ED, Bhatt DL, Cannon CP, et al. Trends in patients hospitalized with heart failure and preserved left ventricular ejection fraction: prevalence, therapies, and outcomes. Circulation. 2012;126:65–75. https://doi.org/10.1161/CIRCULATIONAHA.111.080770.

    Article  PubMed  Google Scholar 

  3. Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE, Colvin MM, et al. 2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of Amer. Circ (New York, NY). 2017;136:e137–61. https://doi.org/10.1161/cir.0000000000000509.

    Article  Google Scholar 

  4. Shah S. Precision medicine for heart failure with preserved ejection fraction: an overview. J Cardiovasc Transl Res. 2017;10:233–44. https://doi.org/10.1007/s12265-017-9756-y.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Anker SD, Butler J, Filippatos G, Ferreira JP, Bocchi E, Bohm M, et al. Empagliflozin in heart failure with a preserved ejection fraction. N Engl J Med. 2021;385:1451–61. https://doi.org/10.1056/NEJMoa2107038.

    Article  CAS  PubMed  Google Scholar 

  6. Rabkin SW, Tang JKK. The utility of growth differentiation factor-15, galectin-3, and sST2 as biomarkers for the diagnosis of heart failure with preserved ejection fraction and compared to heart failure with reduced ejection fraction: a systematic review. Heart Fail Rev. 2021;26:799–812. https://doi.org/10.1007/s10741-020-09913-3.

    Article  CAS  PubMed  Google Scholar 

  7. Moher D, Liberati A, Tetzlaff J, Altman DG, Group TP. Preferred Reporting Items for Systematic Reviews and Meta-Analyses: the PRISMA statement. PLoS Med. 2009;6:e1000097.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Schuett K, Kleber ME, Scharnagl H, Lorkowski S, Marz W, Niessner A, et al. Trimethylamine-N-oxide and heart failure with reduced versus preserved ejection fraction. J Am Coll Cardiol. 2017;70:3202–4. https://doi.org/10.1016/j.jacc.2017.10.064.

    Article  PubMed  Google Scholar 

  9. Higgins J, Thomas J, Chandler J, Cumpston M, Li T, Page M, et al. 2021 Cochrane handbook for systematic reviews of interventions version 6.2.

  10. Bai B, Cheng M, Jiang L, Xu J, Chen H, Xu Y. High neutrophil to lymphocyte ratio and its gene signatures correlate with diastolic dysfunction in heart failure with preserved ejection fraction. Front Cardiovasc Med. 2021;8:614757. https://doi.org/10.3389/fcvm.2021.614757.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Berge K, Lyngbakken MN, Myhre PL, Brynildsen J, Røysland R, Strand H, et al. High-sensitivity cardiac troponin T and N-terminal pro-B-type natriuretic peptide in acute heart failure: data from the ACE 2 study. Clin Biochem. 2021;88:30–6. https://doi.org/10.1016/j.clinbiochem.2020.11.009.

    Article  CAS  PubMed  Google Scholar 

  12. van Wezenbeek J, Canada JM, Ravindra K, Carbone S, Trankle CR, Kadariya D, et al. C-Reactive protein and N-terminal pro-brain natriuretic peptide levels correlate with impaired cardiorespiratory fitness in patients with heart failure across a wide range of ejection fraction . Front Cardiovasc Med 2018;5.

  13. Tromp J, Khan MAF, Mentz RJ, O’Connor CM, Metra M, Dittrich HC, et al. Biomarker profiles of acute heart failure patients with a mid-range ejection fraction. JACC Heart Fail. 2017;5:507–17. https://doi.org/10.1016/j.jchf.2017.04.007.

    Article  PubMed  Google Scholar 

  14. Brouwers FP, De Boer RA, Van Der Harst P, Voors AA, Gansevoort RT, Bakker SJ, et al. Incidence and epidemiology of new onset heart failure with preserved vs. reduced ejection fraction in a community-based cohort: 11-year follow-up of PREVEND. Eur Heart J. 2013;34:1424–31. https://doi.org/10.1093/eurheartj/eht066.

    Article  CAS  PubMed  Google Scholar 

  15. Kanagala P, Arnold JR, Singh A, Chan DCS, Cheng ASH, Khan JN, et al. Characterizing heart failure with preserved and reduced ejection fraction: an imaging and plasma biomarker approach. PLoS ONE. 2020;15:e0232280. https://doi.org/10.1371/journal.pone.0232280.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Moran A, Katz R, Smith NL, Fried LF, Sarnak MJ, Seliger SL, et al. Cystatin C concentration as a predictor of systolic and diastolic heart failure. J Card Fail. 2008;14:19–26. https://doi.org/10.1016/j.cardfail.2007.09.002.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Sinning C, Kempf T, Schwarzl M, Lanfermann S, Ojeda F, Schnabel RB, et al. Biomarkers for characterization of heart failure - distinction of heart failure with preserved and reduced ejection fraction. Int J Cardiol. 2017;227:272–7. https://doi.org/10.1016/j.ijcard.2016.11.110.

    Article  PubMed  Google Scholar 

  18. Grossekettler L, Schmack B, Brockmann C, Wanninger R, Kreusser MM, Frankenstein L, et al. Benefits of peritoneal ultrafiltration in HFpEF and HFrEF patients. BMC Nephrol. 2020;21:179. https://doi.org/10.1186/s12882-020-01777-x.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Kang J, Park JJ, Cho Y-J, Oh I-Y, Park H-A, Lee SE, et al. Predictors and prognostic value of worsening renal function during admission in HFpEF versus HFrEF: data from the KorAHF (Korean Acute Heart Failure) registry. J Am Heart Assoc 2018;7. https://doi.org/10.1161/JAHA.117.007910.

  20. Mitic VT, Stojanovic DR, Deljanin Ilic MZ, Stojanovic MM, Petrovic DB, Ignjatovic AM, et al. Cardiac remodeling biomarkers as potential circulating markers of left ventricular hypertrophy in heart failure with preserved ejection fraction. Tohoku J Exp Med. 2020;250:233–42. https://doi.org/10.1620/tjem.250.233.

    Article  CAS  PubMed  Google Scholar 

  21. Tromp J, Khan MAF, Klip IjT, Meyer S, de Boer RA, Jaarsma T, et al. Biomarker profiles in heart failure patients with preserved and reduced ejection fraction. J Am Heart Assoc 2017;6. https://doi.org/10.1161/JAHA.116.003989.

  22. Janeiro MH, Ramirez MJ, Milagro FI, Martinez JA, Solas M. Implication of trimethylamine N-oxide (TMAO) in disease: potential biomarker or new therapeutic target. Nutrients. 2018;10:1398. https://doi.org/10.3390/nu10101398. This review article discussed dietary sources and metabolic pathways of trimethylamine-N-oxide (TMAO), the possible involvement of TMAO in the etiology of cardiovascular disorders, the importance of TMAO mediating inflammatory processes, and the potential utility of TMAO as a therapeutic target.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Xia C-L, Chu P, Liu Y-X, Qu X-L, Gao X-F, Wang Z-M, et al. ALDH2 rs671 polymorphism and the risk of heart failure with preserved ejection fraction (HFpEF) in patients with cardiovascular diseases. J Hum Hypertens. 2020;34:16–23. https://doi.org/10.1038/s41371-019-0182-2.

    Article  CAS  PubMed  Google Scholar 

  24. Guo F, Qiu X, Tan Z, Li Z, Ouyang D. Plasma trimethylamine n-oxide is associated with renal function in patients with heart failure with preserved ejection fraction. BMC Cardiovasc Disord. 2020;20:394. https://doi.org/10.1186/s12872-020-01669-w.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Hayashi T, Yamashita T, Watanabe H, Kami K, Yoshida N, Tabata T, et al. Gut microbiome and plasma microbiome-related metabolites in patients with decompensated and compensated heart failure. Circ J. 2018;83:182–92. https://doi.org/10.1253/circj.CJ-18-0468. This article demonstrated that plasma concentrations of trimethylamine-N-oxide (TMAO) were increased in heart failure patients, supporting the hypothesis that gut microbiome composition is altered in heart failure patients.

    Article  PubMed  Google Scholar 

  26. Salzano A, Israr MZ, Yazaki Y, Heaney LM, Kanagala P, Singh A, et al. Combined use of trimethylamine N-oxide with BNP for risk stratification in heart failure with preserved ejection fraction: findings from the DIAMONDHFpEF study. Eur J Prev Cardiol. 2020;27:2159–62. https://doi.org/10.1177/2047487319870355.

    Article  PubMed  Google Scholar 

  27. Tanaka T, Narazaki M, Kishimoto T. IL-6 in inflammation, immunity, and disease. Cold Spring Harb Perspect Biol. 2014;6:a016295. https://doi.org/10.1101/cshperspect.a016295.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Arvidsson M, Ahmed A, Bouzina H, Rådegran G. Plasma proteoglycan prolargin in diagnosis and differentiation of pulmonary arterial hypertension. ESC Hear Fail. 2021;8:1230–43.

    Article  Google Scholar 

  29. Lundberg JO, Gladwin MT, Ahluwalia A, Benjamin N, Bryan NS, Butler A, et al. Nitrate and nitrite in biology, nutrition and therapeutics. Nat Chem Biol. 2009;5:865–9. https://doi.org/10.1038/nchembio.260.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Chirinos JA, Akers SR, Trieu L, Ischiropoulos H, Doulias P-T, Tariq A, et al. Heart failure, left ventricular remodeling, and circulating nitric oxide metabolites. J Am Heart Assoc. 2016;5:1–8.

    Article  Google Scholar 

  31. Yu C-M, Fung PC-W, Chan G, Lai KW-H, Wang Q, Lau C-P. Plasma nitric oxide level in heart failure secondary to left ventricular diastolic dysfunction. Am J Cardiol. 2001;88:867–70. https://doi.org/10.1016/S0002-9149(01)01894-X.

    Article  CAS  PubMed  Google Scholar 

  32. Zamani P, French B, Brandimarto JA, Doulias P-T, Javaheri A, Chirinos JA, et al. Effect of heart failure with preserved ejection fraction on nitric oxide metabolites. Am J Cardiol. 2016;118:1855–60. https://doi.org/10.1016/j.amjcard.2016.08.077.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Szatmari T, Dobra K. The role of syndecan-1 in cellular signaling and its effects on heparan sulfate biosynthesis in mesenchymal tumors. Front Oncol. 2013;3:310. https://doi.org/10.3389/fonc.2013.00310. This article discussed the involvement of syndecans in the differentiation process across the epithelial-mesenchyma axis, mainly through their ability to bind to growth factors and modulate their downstream signaling.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Idriss HT, Naismith JH. TNF alpha and the TNF receptor superfamily: structure-function relationship(s). Microsc Res Tech. 2000;50:184–95.

    Article  CAS  PubMed  Google Scholar 

  35. McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Böhm M, et al. 2021 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure: developed by the task force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC) with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur Heart J. 2021;42:3599–726. https://doi.org/10.1093/eurheartj/ehab368.

    Article  CAS  PubMed  Google Scholar 

  36. Chia YC, Kieneker LM, van Hassel G, Binnenmars SH, Nolte IM, van Zanden JJ, et al. Interleukin 6 and development of heart failure with preserved ejection fraction in the general population. J Am Heart Assoc. 2021;10:e018549. https://doi.org/10.1161/JAHA.120.018549.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Yan AT, Yan RT, Cushman M, Redheuil A, Tracy RP, Arnett DK, et al. Relationship of interleukin-6 with regional and global left-ventricular function in asymptomatic individuals without clinical cardiovascular disease: insights from the Multi-Ethnic Study of Atherosclerosis. Eur Heart J. 2010;31:875–82. https://doi.org/10.1093/eurheartj/ehp454. This article demonstrated that in asymptomatic men and women without documentedcardiovascular disease, there is a strong, independent, and inverse relationship between interleukin-6 (IL-6) and regional left ventricular systolic function. This suggests that IL-6 may underlie the pathogenetic link between inflammation, left ventricular dysfunction, and incipient heart failure.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Collier P, Watson CJ, Voon V, Phelan D, Jan A, Mak G, et al. Can emerging biomarkers of myocardial remodelling identify asymptomatic hypertensive patients at risk for diastolic dysfunction and diastolic heart failure? Eur J Heart Fail. 2011;13:1087–95. https://doi.org/10.1093/eurjhf/hfr079.

    Article  CAS  PubMed  Google Scholar 

  39. Hirota H, Yoshida K, Kishimoto T, Taga T. Continuous activation of gp130, a signal-transducing receptor component for interleukin 6-related cytokines, causes myocardial hypertrophy in mice. Proc Natl Acad Sci U S A. 1995;92:4862–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Melendez GC, McLarty JL, Levick SP, Du Y, Janicki JS, Brower GL. Interleukin 6 mediates myocardial fibrosis, concentric hypertrophy, and diastolic dysfunction in rats. Hypertens (Dallas, Tex 1979). 2010;56:225–31. https://doi.org/10.1161/HYPERTENSIONAHA.109.148635.

    Article  CAS  Google Scholar 

  41. Wu C-K, Lee J-K, Chiang F-T, Yang C-H, Huang S-W, Hwang J-J, et al. Plasma levels of tumor necrosis factor-alpha and interleukin-6 are associated with diastolic heart failure through downregulation of sarcoplasmic reticulum Ca2+ ATPase. Crit Care Med. 2011;39:984–92. https://doi.org/10.1097/CCM.0b013e31820a91b9.

    Article  CAS  PubMed  Google Scholar 

  42. Lakhani I, Wong MV, Hung JKF, Gong M, Bin WK, Xia Y, et al. Diagnostic and prognostic value of serum C-reactive protein in heart failure with preserved ejection fraction: a systematic review and meta-analysis. Heart Fail Rev. 2021;26:1141–50. https://doi.org/10.1007/s10741-020-09927-x.

    Article  CAS  PubMed  Google Scholar 

  43. Rabkin S. Evaluating the adverse outcome of subtypes of heart failure with preserved ejection fraction defined by machine learning: a systematic review focused on defining high risk phenogroups. EXCLI J. 2022;21:487–518.

    PubMed  PubMed Central  Google Scholar 

  44. Rabkin SW, Langer A, Ur E, Calciu C-D, Leiter LA. Inflammatory biomarkers CRP, MCP-1, serum amyloid alpha and interleukin-18 in patients with HTN and dyslipidemia: impact of diabetes mellitus on metabolic syndrome and the effect of statin therapy. Hypertens Res. 2013;36:550–8. https://doi.org/10.1038/hr.2012.214.

    Article  CAS  PubMed  Google Scholar 

  45. Reitsma S, Slaaf DW, Vink H, van Zandvoort MAMJ, Oude Egbrink MGA. The endothelial glycocalyx: composition, functions, and visualization. Pflugers Arch. 2007;454:345–59.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Kim Y-H, Nijst P, Kiefer K, Tang WHW. Endothelial glycocalyx as biomarker for cardiovascular diseases: mechanistic and clinical implications. Curr Heart Fail Rep. 2017;14:117–26. https://doi.org/10.1007/s11897-017-0320-5. Syndecan-1 (SDC-1) is a main constituent of endothelial glycocalyx. In patients with heart failure, elevated serum SDC-1 has been associated with worsening cardiac and renal function. This review article summarizes the existing literature on endothelial glycocalyx in cardiovascular diseases and their clinical implications.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Mamic P, Chaikijurajai T, Tang WHW. Gut microbiome - a potential mediator of pathogenesis in heart failure and its comorbidities: state-of-the-art review. J Mol Cell Cardiol. 2021;152:105–17. https://doi.org/10.1016/j.yjmcc.2020.12.001. This review article highlights the role that gut microbial metabolites (including short chain fatty acids, trimethylamine-N-oxide (TMAO), amino acid metabolites, and bile acids) play in heart failure pathophysiology and its potential as a novel therapeutic target in heart failure.

    Article  CAS  PubMed  Google Scholar 

  48. Zuo L, Chuang C-C, Hemmelgarn BT, Best TM. Heart failure with preserved ejection fraction: defining the function of ROS and NO. J Appl Physiol. 2015;119:944–51. https://doi.org/10.1152/japplphysiol.01149.2014.

    Article  CAS  PubMed  Google Scholar 

  49. Shea CM, Price GM, Liu G, Sarno R, Buys ES, Currie MG, et al. Soluble guanylate cyclase stimulator praliciguat attenuates inflammation, fibrosis, and end-organ damage in the Dahl model of cardiorenal failure. Am J Physiol Renal Physiol. 2020;318:F148–59. https://doi.org/10.1152/ajprenal.00247.2019. This article discusses how stimulate of soluble guanylate cyclase by praliciguat may be an effective mechanism for treating diseases linked to nitric oxide deficiency, particularly those associated with cardiac failure.

    Article  CAS  PubMed  Google Scholar 

  50. Redfield MM, Anstrom KJ, Levine JA, Koepp GA, Borlaug BA, Chen HH, et al. Isosorbide mononitrate in heart failure with preserved ejection fraction. N Engl J Med. 2015;373:2314–24. https://doi.org/10.1056/NEJMoa1510774.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Chirinos JA, Londono-Hoyos F, Zamani P, Beraun M, Haines P, Vasim I, et al. Effects of organic and inorganic nitrate on aortic and carotid haemodynamics in heart failure with preserved ejection fraction. Eur J Heart Fail. 2017;19:1507–15. https://doi.org/10.1002/ejhf.885.

    Article  CAS  PubMed  Google Scholar 

  52. Matyas C, Nemeth BT, Olah A, Torok M, Ruppert M, Kellermayer D, et al. Prevention of the development of heart failure with preserved ejection fraction by the phosphodiesterase-5A inhibitor vardenafil in rats with type 2 diabetes. Eur J Heart Fail. 2017;19:326–36. https://doi.org/10.1002/ejhf.711.

    Article  CAS  PubMed  Google Scholar 

  53. Gullestad L, Ueland T, Vinge LE, Finsen A, Yndestad A, Aukrust P. Inflammatory cytokines in heart failure: mediators and markers. Cardiology. 2012;122:23–35. https://doi.org/10.1159/000338166. Inflammatory mediators are important in the pathogenesis of chronic heart failure contributing to cardiac remodeling and peripheral vascular disturbances. This review article argues for the possibility of future therapeutic targets such as mediators in innate immunity, chemokines, and mediators in matrix remodeling.

    Article  CAS  PubMed  Google Scholar 

  54. Deswal A, Petersen NJ, Feldman AM, Young JB, White BG, Mann DL. Cytokines and cytokine receptors in advanced heart failure: an analysis of the cytokine database from the Vesnarinone trial (VEST). Circulation. 2001;103:2055–9.

    Article  CAS  PubMed  Google Scholar 

  55. Nouraei H, Rabkin SW. A new approach to the clinical subclassification of heart failure with preserved ejection fraction. Int J Cardiol. 2021;331:138–43. https://doi.org/10.1016/j.ijcard.2021.01.052.

    Article  PubMed  Google Scholar 

  56. Shah SJ, Katz DH, Selvaraj S, Burke MA, Yancy CW, Gheorghiade M, et al. Phenomapping for novel classification of heart failure with preserved ejection fraction. Circulation. 2015;131:269–79. https://doi.org/10.1161/CIRCULATIONAHA.114.010637.

    Article  PubMed  Google Scholar 

  57. Segar MW, Patel KV, Ayers C, Basit M, Tang WHW, Willett D, et al. Phenomapping of patients with heart failure with preserved ejection fraction using machine learning-based unsupervised cluster analysis. Eur J Heart Fail. 2020;22:148–58. https://doi.org/10.1002/ejhf.1621.

    Article  CAS  PubMed  Google Scholar 

  58. Ge Z, Li A, McNamara J, Dos Remedios C, Lal S. Pathogenesis and pathophysiology of heart failure with reduced ejection fraction: translation to human studies. Heart Fail Rev. 2019;24:743–58. https://doi.org/10.1007/s10741-019-09806-0.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Medicine, University of British Columbia, Vancouver, BC, V6T 1Z4, Canada

    Xi Yao Gui & Simon W. Rabkin

  2. Division of Cardiology, University of British Columbia, 9Th Floor 2775 Laurel St, Vancouver, BC, V5Z 1M9, Canada

    Simon W. Rabkin

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SWR: Conceptualization, methodology, and writing.

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Gui, X.Y., Rabkin, S.W. C-Reactive Protein, Interleukin-6, Trimethylamine-N-Oxide, Syndecan-1, Nitric Oxide, and Tumor Necrosis Factor Receptor-1 in Heart Failure with Preserved Versus Reduced Ejection Fraction: a Meta-Analysis. Curr Heart Fail Rep 20, 1–11 (2023). https://doi.org/10.1007/s11897-022-00584-9

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