Impact of diabetes on serum biomarkers in heart failure with preserved ejection fraction: insights from the TOPCAT trial
Open accessAbstract
AIMS: Diabetes mellitus (DM) is common in heart failure with preserved ejection fraction (HFpEF). Patients with DM and heart failure with reduced ejection fraction have higher levels of cardiac, profibrotic, and proinflammatory biomarkers relative to non-diabetics. Limited data are available regarding the biomarker profiles of HFpEF patients with diabetes (DM) vs. no diabetes (non-DM) and the impact of spironolactone on these biomarkers. This study aims to address such gaps in the literature. METHODS AND RESULTS: Biomarkers were measured at randomization and at 12 months in 248 patients enrolled in Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist's North American cohort. At baseline, DM patients had significantly lower estimated glomerular filtration rate and higher high-sensitivity C-reactive protein, pro-collagen type III amino-terminal peptide, tissue inhibitor of metalloproteinase 1 (TIMP-1), and galectin-3 levels than those without diabetes. There was a significantly larger 12 month increase in levels of high-sensitivity troponin T (hs-TnT), a marker of myocyte death, in DM patients. Elevated pro-collagen type III amino-terminal peptide and galectin-3 levels were associated with an increased risk of the primary outcome (cardiovascular mortality, aborted cardiac arrest, or heart failure hospitalization) in DM patients, but not in those without diabetes. A statistically significant interaction between spironolactone and diabetes status was observed for hs-TnT and for TIMP-1, with greater biomarker reductions among those with diabetes treated with spironolactone. CONCLUSIONS: The presence of diabetes is associated with higher levels of cardiac, profibrotic, and proinflammatory biomarkers in HFpEF. Spironolactone appears to alter the determinants of extracellular matrix remodelling in an anti-fibrotic fashion in patients with diabetes, reflected by changes in hs-TnT and TIMP-1 levels over time.
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Type 2 diabetes is common in patients with HFpEF.
“Type 2 diabetes is common in patients with HFpEF. 4-6”
From Semaglutide versus placebo in people with obesity-related heart failure with preserved ejection fraction: a pooled analysis of the STEP-HFpEF and STEP-HFpEF DM randomised trials (2024) · cites this paper as [6]
The Introduction says diabetes mellitus is a common comorbidity in HFpEF, and the Results report diabetes in 116 of 248 patients (46.8%) in the biomarker cohort. The paper does not distinguish type 2 diabetes from other types, so it supports the prevalence claim for diabetes generally but not the specified subtype. (LLM, conf=0.82)
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Cites
Trends in Prevalence and Outcome of Heart Failure with Preserved Ejection Fraction
Owan, T., Hodge, D. O., Herges, R. M., Jacobsen, S. J., Roger, V. L., & Redfield, M. M. (2006) · New England Journal of Medicine · doi:10.1056/nejmoa052256 · Cited by 4,191 · see citing works
A Novel Paradigm for Heart Failure With Preserved Ejection Fraction
Paulus, W. J., & Tschöpe, C. (2013) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2013.02.092 · Cited by 3,564 · see citing works
Spironolactone for heart failure with preserved ejection fraction
Pitt, B., Pfeffer, M. A., Assmann, S. F., Boineau, R., Anand, I. S., Claggett, B., Clausell, N., Desai, A. S., Diaz, R., Fleg, J. L., et al. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1313731 · Cited by 2,809 · see citing works
Self-citationJia, G., Hill, M. A., & Sowers, J. R. (2018) · Circulation Research · doi:10.1161/circresaha.117.311586 · Cited by 1,838 · see citing works
New type of cardiomyopathy associated with diabetic glomerulosclerosis
Rubler, S., Dlugash, J., Yuceoglu, Y. Z., Kumral, T., Branwood, A. W., & Grishman, A. (1972) · The American Journal of Cardiology · doi:10.1016/0002-9149(72)90595-4 · Cited by 1,835 · see citing works
Type 2 diabetes and incidence of cardiovascular diseases: a cohort study in 1.9 million people
Shah, A. D., Langenberg, C., Rapsomaniki, E., Denaxas, S., Pujades-Rodriguez, M., Gale, C. P., Deanfield, J., Smeeth, L., Timmis, A., & Hemingway, H. (2015) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(14)70219-0 · Cited by 1,225 · see citing works
Pfeffer, M. A., Claggett, B. L., Assmann, S. F., Boineau, R., Anand, I. S., Clausell, N., Desai, A. S., Díaz, R., Fleg, J. L., Gordeev, I. G., et al. (2014) · Circulation · doi:10.1161/circulationaha.114.013255 · Cited by 1,066 · see citing works
Self-citationSharma, U. C., Pokharel, S., van Brakel, T. J., van Berlo, J. H., Cleutjens, J. P. M., Schroen, B. L. M., André, S., Crijns, H. J. G. M., Gabius, H., Maessen, J. G., et al. (2004) · Circulation · doi:10.1161/01.cir.0000147181.65298.4d · Cited by 949 · see citing works
Zannad, F. M., Alla, F., Dousset, B., Pérez, A. J. P., & Pitt, B. (2000) · Circulation · doi:10.1161/01.cir.102.22.2700 · Cited by 946 · see citing works
Self-citationZile, M. R., Baicu, C. F., S. Ikonomidis, J., Stroud, R. E., Nietert, P. J., Bradshaw, A. D., Slater, R., Palmer, B. M., Van Buren, P., Meyer, M., et al. (2015) · Circulation · doi:10.1161/circulationaha.114.013215 · Cited by 681 · see citing works
Self-citationNoncardiac comorbidities in heart failure with reduced versus preserved ejection fraction
Mentz, R. J., Kelly, J. P., von Lueder, T. G., Voors, A. A., Lam, C. S. P., Cowie, M. R., Kjeldsen, K., Jankowska, E. A., Atar, D., Butler, J., et al. (2014) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2014.08.036 · Cited by 546 · see citing works
Self-citationKristensen, S. L., Preiss, D., Jhund, P. S., Squire, I., Cardoso, J. S., Merkely, B., Martinez, F., Starling, R. C., Desai, A. S., Lefkowitz, M. P., et al. (2016) · Circulation Heart Failure · doi:10.1161/circheartfailure.115.002560 · Cited by 359 · see citing works
Self-citationDesai, A. S., Lewis, E. F., Li, R., Solomon, S. D., Assmann, S. F., Boineau, R., Clausell, N., Díaz, R., Fleg, J. L., Гордеев, И. Г., et al. (2011) · American Heart Journal · doi:10.1016/j.ahj.2011.09.007 · Cited by 274 · see citing works
Self-citationSpironolactone Metabolites in TOPCAT — New Insights into Regional Variation
de Denus, S., O’Meara, E., Desai, A. S., Claggett, B. L., Lewis, E. F., Leclair, G., Jutras, M., Lavoie, J., Solomon, S. D., Pitt, B., et al. (2017) · New England Journal of Medicine · doi:10.1056/nejmc1612601 · Cited by 274 · see citing works
Self-citationKlappacher, G., Franzen, P., Haab, D., Mehrabi, M. R., Binder, M., Plesch, K., Pacher, R., Grimm, M. F., Pribill, I., Eichler, H., et al. (1995) · The American Journal of Cardiology · doi:10.1016/s0002-9149(99)80686-9 · Cited by 258 · see citing works
López‐Andrés, N., Rossignol, P., Iraqi, W., et al. (2011) · European Journal of Heart Failure · doi:10.1093/eurjhf/hfr151 · Cited by 226 · see citing works
Tang, W. H. W., Shrestha, K. L., Shao, Z., Borowski, A. G., Troughton, R. W., Thomas, J. D., & Klein, A. L. (2011) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2011.03.056 · Cited by 209 · see citing works
Kristensen, S. L., Mogensen, U. M., Jhund, P. S., Petrie, M. C., Preiss, D., Win, S., Køber, L., McKelvie, R. S., Zile, M. R., Anand, I. S., et al. (2017) · Circulation · doi:10.1161/circulationaha.116.024593 · Cited by 202 · see citing works
Self-citationEdelmann, F., Holzendorf, V., Wachter, R., et al. (2014) · European Journal of Heart Failure · doi:10.1002/ejhf.203 · Cited by 176 · see citing works
Anand, I. S., Claggett, B. L., Liu, J., Shah, A. M., Rector, T. S., Shah, S. J., Desai, A. S., O’Meara, E., Fleg, J. L., Pfeffer, M. A., et al. (2017) · JACC Heart Failure · doi:10.1016/j.jchf.2016.11.015 · Cited by 176 · see citing works
Self-citationSundström, J. (2004) · European Heart Journal · doi:10.1016/j.ehj.2004.05.029 · Cited by 163 · see citing works
Martos, R., Baugh, J. A., Ledwidge, M. T., O’Loughlin, C., Murphy, N. F., Conlon, C. M., Patle, A. K., Donnelly, S. C., & McDonald, K. (2009) · European Journal of Heart Failure · doi:10.1093/eurjhf/hfn036 · Cited by 134 · see citing works
Identifying Novel Biomarkers for Cardiovascular Events or Death in People With Dysglycemia
Gerstein, H. C., Paré, G., McQueen, M. J., Haenel, H., Lee, S. F., Pogue, J., Maggioni, A. P., Yusuf, S., & Hess, S. (2015) · Circulation · doi:10.1161/circulationaha.115.015744 · Cited by 69 · see citing works
Sharma, A., Demissei, B. G., Tromp, J., Hillege, H. L., Cleland, J. G. F., O’Connor, C. M., Metra, M., Ponikowski, P. P., Teerlink, J. R., Davison, B. A., et al. (2017) · European Journal of Heart Failure · doi:10.1002/ejhf.912 · Cited by 64 · see citing works
Impact of diabetes on the predictive value of heart failure biomarkers
Alonso, N., Lupón, J., Barallat, J., de Antonio, M., Domingo, M., Zamora, E., Moliner, P., Galán, A., Santesmases, J., Pastor, C., et al. (2016) · Cardiovascular Diabetology · doi:10.1186/s12933-016-0470-x · Cited by 62 · see citing works
Myhre, P. L., O’Meara, E., Claggett, B. L., de Denus, S., Jarolı́m, P., Anand, I. S., Beldhuis, I. E., Fleg, J. L., Lewis, E. F., Pitt, B., et al. (2018) · Circulation Heart Failure · doi:10.1161/circheartfailure.118.005312 · Cited by 54 · see citing works
Self-citationGiorda, C. B., Carnà, P., Salomone, M., Picariello, R., Costa, G., Tartaglino, B., & Gnavi, R. (2018) · Acta Diabetologica · doi:10.1007/s00592-018-1142-y · Cited by 46 · see citing works
LaRocca, G., Aspelund, T., Greve, A. M., Eiríksdóttir, G., Acharya, T., Þorgeirsson, G., Harris, T. B., Launer, L. J., Gudnason, V. G., & Arai, A. E. (2017) · European Heart Journal · doi:10.1093/eurheartj/ehx510 · Cited by 29 · see citing works
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Butler, J., Shah, S. J., Petrie, M. C., Borlaug, B. A., Abildstrøm, S. Z., Davies, M. J., Hovingh, G. K., Kitzman, D. W., Møller, D. V., Verma, S., et al. (2024) · The Lancet · doi:10.1016/s0140-6736(24)00469-0 · Cited by 386 · see citing works
Filippatos, G., Butler, J., Farmakis, D., Zannad, F., Ofstad, A. P., Ferreira, J. P., Green, J. B., Rosenstock, J., Schnaidt, S., Brueckmann, M., et al. (2022) · Circulation · doi:10.1161/circulationaha.122.059785 · Cited by 131 · see citing works
Seferović, P., Farmakis, D., Bayes-Genis, A., Ben Gal, T., Böhm, M., Chioncel, O., Ferrari, R., Filippatos, G., Hill, L., Jankowska, E., et al. (2022) · European Journal of Heart Failure · doi:10.1002/ejhf.2575 · Cited by 24 · see citing works
- Authors
- De Marco, C., Claggett, B. L., de Denus, S., Zile, M. R., Huynh, T., Desai, A. S., Sirois, M. G., Solomon, S. D., Pitt, B., Rouleau, J. L., Pfeffer, M. A., & O'Meara, E.
- Affiliations
- Division of Cardiology, Montreal Heart Institute and Université de Montréal , 5000 rue Bélanger, Montreal, QC, H1T 1C8 ,
- Brigham and Women's Hospital (US)
- Medical University of South Carolina (US)
- McGill University Health Centre (CA)
- Montreal Heart Institute (CA)
- University of Michigan (US)
- ORCID
- Venue
- ESC Heart Failure
- Publisher
- Oxford University Press (OUP)
- Published
- 2021-01-12
- Volume
- 8
- Issue
- 2
- Pages
- 1130-1138
- ISSN
- 2055-5822 (ISSN-L)
- PMC
- PMC8006665
- OpenAlex
- W3120111174
- Cited by
- 29
- References
- 28
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 4 · 2023: 8 · 2022: 9 · 2021: 4
- FWCI
- 4.19
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- ESC Heart Failure (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Deep Blue (University of Michigan) (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Heart, Lung, and Blood Institute (NCT00094302)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Failure Treatment and Management
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Function and Risk Factors
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
- Keywords
- diabetes mellitus, heart failure with preserved ejection fraction, serum biomarkers, spironolactone, TOPCAT trial, high-sensitivity troponin T, TIMP-1, galectin-3, C-reactive protein, extracellular matrix remodeling, myocardial fibrosis, cardiovascular mortality, heart failure hospitalization
- MeSH terms
- Mineralocorticoid Receptor Antagonists, Diabetes Mellitus, Heart Failure, Humans, Stroke Volume, Biomarkers, Tissue Inhibitor of Metalloproteinase-1
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