Top

Published in:

Open Access 01-09-2021 | Heart Failure

Diagnostic and prognostic value of serum C-reactive protein in heart failure with preserved ejection fraction: a systematic review and meta-analysis

Authors: Ishan Lakhani, Michelle Vangi Wong, Joshua Kai Fung Hung, Mengqi Gong, Khalid Bin Waleed, Yunlong Xia, Sharen Lee, Leonardo Roever, Tong Liu, Gary Tse, Keith Sai Kit Leung, Ka Hou Christien Li

Published in: Heart Failure Reviews | Issue 5/2021

Abstract

Heart failure (HF) is a major epidemic with rising morbidity and mortality rates that encumber global healthcare systems. While some studies have demonstrated the value of CRP in predicting (i) the development of HFpEF and (ii) long-term clinical outcomes in HFpEF patients, others have shown no such correlation. As a result, we conducted the following systematic review and meta-analysis to assess both the diagnostic and prognostic role of CRP in HFpEF. PubMed and Embase were searched for studies that assess the relationship between CRP and HFpEF using the following search terms: (((C-reactive protein) AND ((preserved ejection fraction) OR (diastolic heart failure))). The search period was from the start of database to August 6, 2019, with no language restrictions. A total of 312 and 233 studies were obtained from PubMed and Embase respectively, from which 19 studies were included. Our meta-analysis demonstrated the value of a high CRP in predicting the development of not only new onset HFpEF (HR: 1.08; 95% CI: 1.00–1.16; P = 0.04; I² = 22%), but also an increased risk of cardiovascular mortality when used as a categorical (HR: 2.52; 95% CI: 1.61–3.96; P < 0.0001; I² = 19%) or a continuous variable (HR: 1.24; 95% CI: 1.04–1.47; P = 0.01; I² = 28%), as well as all-cause mortality when used as a categorical (HR: 1.78; 95% CI: 1.53–2.06; P < 0.00001; I² = 0%) or a continuous variable: (HR: 1.06; 95% CI: 1.02–1.06; P = 0.003; I² = 61%) in HFpEF patients. CRP can be used as a biomarker to predict the development of HFpEF and long-term clinical outcomes in HFpEF patients, in turn justifying its use as a simple, accessible parameter to guide clinical management in this patient population. However, more prospective studies are still required to not only explore the utility and dynamicity of CRP in HFpEF but also to determine whether risk stratification algorithms incorporating CRP actually provide a material benefit in improving patient prognosis.

Available only for authorised users

Ponikowski P, Voors AA, Anker SD, Bueno H, Cleland JG, Coats AJ, Falk V, González-Juanatey JR, Harjola VP, Jankowska EA, Jessup M, Linde C, Nihoyannopoulos P, Parissis JT, Pieske B, Riley JP, Rosano GM, Ruilope LM, Ruschitzka F, Rutten FH, van der Meer P, Members ATF, Reviewers D (2016) 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: the Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur J Heart Fail 18(8):891–975. https://doi.org/10.1002/ejhf.592CrossRefPubMed

Abernethy A, Raza S, Sun JL, Anstrom KJ, Tracy R, Steiner J, VanBuren P, LeWinter MM (2018) Pro-inflammatory biomarkers in stable versus acutely decompensated heart failure with preserved ejection fraction. J Am Heart Assoc 7(8). https://doi.org/10.1161/JAHA.117.007385

van Wezenbeek J, Canada JM, Ravindra K, Carbone S, Trankle CR, Kadariya D, Buckley LF, Del Buono M, Billingsley H, Viscusi M, Wohlford GF, Arena R, Van Tassell B, Abbate A (2018) 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 5:178. https://doi.org/10.3389/fcvm.2018.00178CrossRefPubMedPubMedCentral

Moher D, Shamseer L, Clarke M, Ghersi D, Liberati A, Petticrew M, Shekelle P, Stewart LA, Group P-P (2015) Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement. Syst Rev 4:1. https://doi.org/10.1186/2046-4053-4-1CrossRefPubMedPubMedCentral

Brouwers FP, van Gilst WH, Damman K, van den Berg MP, Gansevoort RT, Bakker SJ, Hillege HL, van Veldhuisen DJ, van der Harst P, de Boer RA (2014) Clinical risk stratification optimizes value of biomarkers to predict new-onset heart failure in a community-based cohort. Circ Heart Fail 7(5):723–731. https://doi.org/10.1161/CIRCHEARTFAILURE.114.001185CrossRefPubMed

de Boer RA, Nayor M, deFilippi CR, Enserro D, Bhambhani V, Kizer JR, Blaha MJ, Brouwers FP, Cushman M, Lima JAC, Bahrami H, van der Harst P, Wang TJ, Gansevoort RT, Fox CS, Gaggin HK, Kop WJ, Liu K, Vasan RS, Psaty BM, Lee DS, Hillege HL, Bartz TM, Benjamin EJ, Chan C, Allison M, Gardin JM, Januzzi JL, Shah SJ, Levy D, Herrington DM, Larson MG, van Gilst WH, Gottdiener JS, Bertoni AG, Ho JE (2018) Association of cardiovascular biomarkers with incident heart failure with preserved and reduced ejection fraction. JAMA Cardiol 3(3):215–224. https://doi.org/10.1001/jamacardio.2017.4987CrossRefPubMedPubMedCentral

Kalogeropoulos A, Georgiopoulou V, Psaty BM, Rodondi N, Smith AL, Harrison DG, Liu Y, Hoffmann U, Bauer DC, Newman AB, Kritchevsky SB, Harris TB, Butler J, Investigators HAS (2010) Inflammatory markers and incident heart failure risk in older adults: the Health ABC (Health, Aging, and Body Composition) study. J Am Coll Cardiol 55(19):2129–2137. https://doi.org/10.1016/j.jacc.2009.12.045CrossRefPubMedPubMedCentral

Silverman MG, Patel B, Blankstein R, Lima JA, Blumenthal RS, Nasir K, Blaha MJ (2016) Impact of race, ethnicity, and multimodality biomarkers on the incidence of new-onset heart failure with preserved ejection fraction (from the Multi-Ethnic Study of Atherosclerosis). Am J Cardiol 117(9):1474–1481. https://doi.org/10.1016/j.amjcard.2016.02.017CrossRefPubMedPubMedCentral

Tromp J, Khan MA, Klip IT, Meyer S, de Boer RA, Jaarsma T, Hillege H, van Veldhuisen DJ, van der Meer P, Voors AA (2017) Biomarker profiles in heart failure patients with preserved and reduced ejection fraction. J Am Heart Assoc 6(4). https://doi.org/10.1161/JAHA.116.003989

10.

Koller L, Kleber M, Goliasch G, Sulzgruber P, Scharnagl H, Silbernagel G, Grammer T, Delgado G, Tomaschitz A, Pilz S, März W, Niessner A (2014) C-reactive protein predicts mortality in patients referred for coronary angiography and symptoms of heart failure with preserved ejection fraction. Eur J Heart Fail 16(7):758–766. https://doi.org/10.1002/ejhf.104CrossRefPubMed

11.

Otsuka K, Nakanishi K, Shimada K, Nakamura H, Inanami H, Nishioka H, Fujimoto K, Kasayuki N, Yoshiyama M (2018) Associations of sensitive cardiac troponin-I with left ventricular morphology, function and prognosis in end-stage renal disease patients with preserved ejection fraction. Heart Vessel 33(11):1334–1342. https://doi.org/10.1007/s00380-018-1192-7CrossRef

12.

Sugano A, Seo Y, Ishizu T, Sai S, Yamamoto M, Hamada-Harimura Y, Machino-Ohtsuka T, Obara K, Nishi I, Aonuma K, Nogami A (2019) Soluble ST2 and brain natriuretic peptide predict different mode of death in patients with heart failure and preserved ejection fraction. J Cardiol 73(4):326–332. https://doi.org/10.1016/j.jjcc.2018.10.012CrossRefPubMed

13.

Chen WS, Chen SJ, Lee CC, Cherng WJ, Liu MH, Wang CH (2013) Plasma P-selectin predicts long-term cardiovascular events in hospitalized patients with suspected coronary artery disease and preserved left ventricular function: a 10-year follow-up study. Biom J 36(3):137–143. https://doi.org/10.4103/2319-4170.113231CrossRef

14.

Sabatine MS, Morrow DA, Jablonski KA, Rice MM, Warnica JW, Domanski MJ, Hsia J, Gersh BJ, Rifai N, Ridker PM, Pfeffer MA, Braunwald E, Investigators P (2007) Prognostic significance of the Centers for Disease Control/American Heart Association high-sensitivity C-reactive protein cut points for cardiovascular and other outcomes in patients with stable coronary artery disease. Circulation 115(12):1528–1536. https://doi.org/10.1161/CIRCULATIONAHA.106.649939CrossRefPubMed

15.

Vrsalović M, Vučur K, Car B, Krčmar T, Vrsalović Presečki A (2015) C-reactive protein, renal function, and cardiovascular outcome in patients with symptomatic peripheral artery disease and preserved left ventricular systolic function. Croat Med J 56(4):351–356. https://doi.org/10.3325/cmj.2015.56.351CrossRefPubMedPubMedCentral

16.

Hirata Y, Yamamoto E, Tokitsu T, Kusaka H, Fujisue K, Kurokawa H, Sugamura K, Maeda H, Tsujita K, Yamamuro M, Kaikita K, Hokimoto S, Sugiyama S, Ogawa H (2015) Reactive oxidative metabolites are associated with the severity of heart failure and predict future cardiovascular events in heart failure with preserved left ventricular ejection fraction. Int J Cardiol 179:305–308. https://doi.org/10.1016/j.ijcard.2014.11.018CrossRefPubMed

17.

Matsubara J, Sugiyama S, Nozaki T, Akiyama E, Matsuzawa Y, Kurokawa H, Maeda H, Fujisue K, Sugamura K, Yamamoto E, Matsui K, Jinnouchi H, Ogawa H (2014) Incremental prognostic significance of the elevated levels of pentraxin 3 in patients with heart failure with normal left ventricular ejection fraction. J Am Heart Assoc 3(4). https://doi.org/10.1161/JAHA.114.000928

18.

Aramburu-Bodas Ó, García-Casado B, Salamanca-Bautista P, Guisado-Espartero ME, Arias-Jiménez JL, Barco-Sánchez A, Santamaría-González JC, Formiga F, Montero-Pérez-Barquero M, Manzano L (2015) Relationship between osteoprotegerin and mortality in decompensated heart failure with preserved ejection fraction. J Cardiovasc Med (Hagerstown) 16(6):438–443. https://doi.org/10.2459/JCM.0000000000000229CrossRef

19.

Lourenço P, Pereira J, Ribeiro A, Ferreira-Coimbra J, Barroso I, Guimarães JT, Leite-Moreira A, Bettencourt P (2019) C-reactive protein decrease associates with mortality reduction only in heart failure with preserved ejection fraction. J Cardiovasc Med (Hagerstown) 20(1):23–29. https://doi.org/10.2459/JCM.0000000000000726CrossRef

20.

AlBadri A, Lai K, Wei J, Landes S, Mehta PK, Li Q, Johnson D, Reis SE, Kelsey SF, Bittner V, Sopko G, Shaw LJ, Pepine CJ, Bairey Merz CN (2017) Inflammatory biomarkers as predictors of heart failure in women without obstructive coronary artery disease: a report from the NHLBI-sponsored Women’s Ischemia Syndrome Evaluation (WISE). PLoS One 12(5):e0177684. https://doi.org/10.1371/journal.pone.0177684CrossRefPubMedPubMedCentral

21.

Imai R, Uemura Y, Okumura T, Takemoto K, Uchikawa T, Koyasu M, Ishikawa S, Iwamiya S, Ozaki Y, Shibata R, Watarai M, Murohara T (2017) Impact of red blood cell distribution width on non-cardiac mortality in patients with acute decompensated heart failure with preserved ejection fraction. J Cardiol 70(6):591–597. https://doi.org/10.1016/j.jjcc.2017.03.010CrossRefPubMed

22.

Matsushita K, Harada K, Miyazaki T, Miyamoto T, Kohsaka S, Iida K, Tanimoto S, Takei M, Hosoda T, Yamamoto Y, Shiraishi Y, Yoshino H, Yamamoto T, Nagao K, Takayama M (2019) Different prognostic associations of beta-blockers and diuretics in heart failure with preserved ejection fraction with versus without high blood pressure. J Hypertens 37(3):643–649. https://doi.org/10.1097/HJH.0000000000001932CrossRefPubMed

23.

Sanders-van Wijk S, van Empel V, Davarzani N, Maeder MT, Handschin R, Pfisterer ME, Brunner-La Rocca HP, investigators T-C (2015) Circulating biomarkers of distinct pathophysiological pathways in heart failure with preserved vs. reduced left ventricular ejection fraction. Eur J Heart Fail 17 (10):1006–1014. doi:https://doi.org/10.1002/ejhf.414

24.

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

25.

Lakhani I, Leung KSK, Tse G, Lee APW (2019) Novel mechanisms in heart failure with preserved, midrange, and reduced ejection fraction. Front Physiol 10:874. https://doi.org/10.3389/fphys.2019.00874CrossRefPubMedPubMedCentral

26.

Paulus WJ, Tschöpe C (2013) A novel paradigm for heart failure with preserved ejection fraction: comorbidities drive myocardial dysfunction and remodeling through coronary microvascular endothelial inflammation. J Am Coll Cardiol 62(4):263–271. https://doi.org/10.1016/j.jacc.2013.02.092CrossRefPubMed

27.

Singh U, Devaraj S, Vasquez-Vivar J, Jialal I (2007) C-reactive protein decreases endothelial nitric oxide synthase activity via uncoupling. J Mol Cell Cardiol 43(6):780–791. https://doi.org/10.1016/j.yjmcc.2007.08.015CrossRefPubMedPubMedCentral

28.

Adukauskienė D, Čiginskienė A, Adukauskaitė A, Pentiokinienė D, Šlapikas R, Čeponienė I (2016) Clinical relevance of high sensitivity C-reactive protein in cardiology. Medicina (Kaunas) 52(1):1–10. https://doi.org/10.1016/j.medici.2015.12.001CrossRef

29.

Greenland P, Alpert JS, Beller GA, Benjamin EJ, Budoff MJ, Fayad ZA, Foster E, Hlatky MA, Hodgson JM, Kushner FG, Lauer MS, Shaw LJ, Smith SC, Taylor AJ, Weintraub WS, Wenger NK, Jacobs AK, Anderson JL, Albert N, Buller CE, Creager MA, Ettinger SM, Guyton RA, Halperin JL, Hochman JS, Nishimura R, Ohman EM, Page RL, Stevenson WG, Tarkington LG, Yancy CW, Foundation ACoC, Association AH (2010) 2010 ACCF/AHA guideline for assessment of cardiovascular risk in asymptomatic adults: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 56(25):e50–e103. https://doi.org/10.1016/j.jacc.2010.09.001CrossRefPubMed

30.

Silva D, Pais de Lacerda A (2012) High-sensitivity C-reactive protein as a biomarker of risk in coronary artery disease. Rev Port Cardiol 31(11):733–745. https://doi.org/10.1016/j.repc.2012.02.018CrossRefPubMed

31.

Ridker PM, Glynn RJ, Hennekens CH (1998) C-reactive protein adds to the predictive value of total and HDL cholesterol in determining risk of first myocardial infarction. Circulation 97(20):2007–2011. https://doi.org/10.1161/01.cir.97.20.2007CrossRefPubMed

32.

Salazar J, Martínez MS, Chávez M, Toledo A, Añez R, Torres Y, Apruzzese V, Silva C, Rojas J, Bermúdez V (2014) C-reactive protein: clinical and epidemiological perspectives. Cardiol Res Pract 2014:605810. https://doi.org/10.1155/2014/605810CrossRefPubMedPubMedCentral

33.

Wener MH, Daum PR, McQuillan GM (2000) The influence of age, sex, and race on the upper reference limit of serum C-reactive protein concentration. J Rheumatol 27(10):2351–2359PubMed

Title: Diagnostic and prognostic value of serum C-reactive protein in heart failure with preserved ejection fraction: a systematic review and meta-analysis
Authors: Ishan Lakhani
Michelle Vangi Wong
Joshua Kai Fung Hung
Mengqi Gong
Khalid Bin Waleed
Yunlong Xia
Sharen Lee
Leonardo Roever
Tong Liu
Gary Tse
Keith Sai Kit Leung
Ka Hou Christien Li
Publication date: 01-09-2021
Publisher: Springer US
Keyword: Heart Failure
Published in: Heart Failure Reviews / Issue 5/2021
Print ISSN: 1382-4147
Electronic ISSN: 1573-7322
DOI: https://doi.org/10.1007/s10741-020-09927-x

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Diagnostic and prognostic value of serum C-reactive protein in heart failure with preserved ejection fraction: a systematic review and meta-analysis

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 5/2021

Environmentally responsive hydrogels for repair of cardiovascular tissue

Effects of statins on the biological features of mesenchymal stem cells and therapeutic implications

The role of non-invasive devices for the telemonitoring of heart failure patients

Anthracycline-induced cardiotoxicity: mechanisms of action, incidence, risk factors, prevention, and treatment

The Elabela-APJ axis: a promising therapeutic target for heart failure

Cost-effectiveness analyses of sacubitril-valsartan for heart failure