Top

Open Access 07-11-2024 | Type 2 Diabetes | Article

NT-proBNP improves prediction of cardiorenal complications in type 2 diabetes: the Hong Kong Diabetes Biobank

Authors: Ronald C. W. Ma, Claudia H. T. Tam, Yong Hou, Eric S. H. Lau, Risa Ozaki, Juliana N. M. Lui, Elaine Chow, Alice P. S. Kong, Chuiguo Huang, Alex C. W. Ng, Erik G. Fung, Andrea O. Y. Luk, Wing Yee So, Cadmon K. P. Lim, Juliana C. N. Chan, for the Hong Kong Diabetes Biobank Study Group

Published in: Diabetologia

Abstract

Aims/hypothesis

N-terminal pro B-type natriuretic peptide (NT-proBNP) is a natriuretic peptide that is strongly associated with congestive heart failure (CHF). The utility of NT-proBNP for prediction of cardiovascular events and renal endpoints, compared with clinical risk factors, has not been evaluated in detail. We hypothesise that NT-proBNP can improve risk stratification and prediction of cardiorenal events in type 2 diabetes, beyond that provided by clinical risk factors.

Methods

NT-proBNP was measured in 1993 samples from the Hong Kong Diabetes Biobank, a multicentre prospective diabetes cohort and biobank. A cut-off of ≥125 pg/ml was used to define elevated NT-proBNP. Associations between elevated NT-proBNP and incident cardiovascular and renal endpoints were examined using Cox regression, adjusted for sex, age and duration of diabetes, as well as other covariates. Prognostic and incremental predictive values of NT-proBNP in diabetes cardiorenal complications, compared with those of the Joint Asia Diabetes Evaluation risk equations for CHD, CHF and kidney failure, were evaluated using the concordance index (C index), net reclassification improvement index, integrated discrimination improvement index and relative integrated discrimination improvement index.

Results

A total of 24.7% of participants had elevated NT-proBNP. Participants with elevated NT-proBNP at baseline had a more adverse cardiometabolic profile, with 2–4-fold higher frequency of complications at baseline. Adjusting for age at baseline, sex and duration of diabetes, elevated NT-proBNP was associated with incident atrial fibrillation (HR 4.64 [95% CI 2.44, 8.85]), CHD (HR 4.21 [2.46, 7.21]), CVD (HR 3.32 [2.20, 5.01]) and CHF (HR 4.18 [2.18, 8.03]; all p<0.001). All these associations remained significant after further adjustment for additional covariates. Elevated NT-proBNP had good discriminative ability for various cardiorenal endpoints, with C index of 0.83 (95% CI 0.76, 0.90) for CHD, 0.88 (0.81, 0.94) for atrial fibrillation, 0.89 (0.83, 0.95) for CHF, 0.81 (0.77, 0.84) for 40% drop in eGFR and 0.88 (0.84, 0.92) for kidney failure. Models incorporating NT-proBNP had improved prediction compared with established clinical risk models. Sensitivity analyses including alternative cut-off of NT-proBNP, as well as use of other risk engines of CHD, yielded similar results.

Conclusions/interpretation

NT-proBNP demonstrated a promising ability to serve as a prognostic marker for a variety of cardiorenal complications in type 2 diabetes. Considering NT-proBNP in clinical assessments could potentially help identify high-risk individuals who may benefit from more intensive therapies.

Graphical Abstract

Available only for authorised users

de Boer IH, Khunti K, Sadusky T et al (2022) Diabetes management in chronic kidney disease: a consensus report by the American Diabetes Association (ADA) and Kidney Disease: Improving Global Outcomes (KDIGO). Kidney Int 102(5):974–989. https://doi.org/10.1016/j.kint.2022.08.012CrossRefPubMed

Davies MJ, Aroda VR, Collins BS et al (2022) Management of hyperglycaemia in type 2 diabetes, 2022. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetologia 65(12):1925–1966. https://doi.org/10.1007/s00125-022-05787-2CrossRefPubMedPubMedCentral

Ahmad A, Lim LL, Morieri ML et al (2024) Precision prognostics for cardiovascular disease in type 2 diabetes: a systematic review and meta-analysis. Commun Med (Lond) 4(1):11. https://doi.org/10.1038/s43856-023-00429-zCrossRefPubMed

Young KG, McInnes EH, Massey RJ et al (2023) Treatment effect heterogeneity following type 2 diabetes treatment with GLP1-receptor agonists and SGLT2-inhibitors: a systematic review. Commun Med (Lond) 3(1):131. https://doi.org/10.1038/s43856-023-00359-wCrossRefPubMed

Dennis JM, Young KG, McGovern AP et al (2022) Development of a treatment selection algorithm for SGLT2 and DPP-4 inhibitor therapies in people with type 2 diabetes: a retrospective cohort study. Lancet Digit Health 4(12):e873–e883. https://doi.org/10.1016/S2589-7500(22)00174-1CrossRefPubMed

Chung WK, Erion K, Florez JC et al (2020) Precision medicine in diabetes: a consensus report from the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care 43(7):1617–1635. https://doi.org/10.2337/dci20-0022CrossRefPubMedPubMedCentral

Tobias DK, Merino J, Ahmad A et al (2023) Second international consensus report on gaps and opportunities for the clinical translation of precision diabetes medicine. Nat Med 29(10):2438–2457. https://doi.org/10.1038/s41591-023-02502-5CrossRefPubMedPubMedCentral

Stevens RJ, Kothari V, Adler AI, Stratton IM, United Kingdom Prospective Diabetes Study (UKPDS) Group (2001) The UKPDS risk engine: a model for the risk of coronary heart disease in type II diabetes (UKPDS 56). Clin Sci (Lond) 101(6):671–679. https://doi.org/10.1042/cs1010671CrossRefPubMed

Khera AV, Chaffin M, Aragam KG et al (2018) Genome-wide polygenic scores for common diseases identify individuals with risk equivalent to monogenic mutations. Nat Genet 50(9):1219–1224. https://doi.org/10.1038/s41588-018-0183-zCrossRefPubMedPubMedCentral

10.

Tam CHT, Lim CKP, Luk AOY et al (2021) Development of genome-wide polygenic risk scores for lipid traits and clinical applications for dyslipidemia, subclinical atherosclerosis, and diabetes cardiovascular complications among East Asians. Genome Med 13(1):29. https://doi.org/10.1186/s13073-021-00831-zCrossRefPubMedPubMedCentral

11.

Morieri ML, Gao H, Pigeyre M et al (2018) Genetic tools for coronary risk assessment in type 2 diabetes: a cohort study from the ACCORD clinical trial. Diabetes Care 41(11):2404–2413. https://doi.org/10.2337/dc18-0709CrossRefPubMedPubMedCentral

12.

Jin Q, Luk AO, Lau ESH et al (2022) Nonalbuminuric diabetic kidney disease and risk of all-cause mortality and cardiovascular and kidney outcomes in type 2 diabetes: findings from the Hong Kong Diabetes Biobank. Am J Kidney Dis 80(2):196-206 e191. https://doi.org/10.1053/j.ajkd.2021.11.011CrossRefPubMed

13.

Mueller C, McDonald K, de Boer RA et al (2019) Heart Failure Association of the European Society of Cardiology practical guidance on the use of natriuretic peptide concentrations. Eur J Heart Fail 21(6):715–731. https://doi.org/10.1002/ejhf.1494CrossRefPubMed

14.

Tsutsui H, Albert NM, Coats AJS et al (2023) Natriuretic peptides: role in the diagnosis and management of heart failure: a scientific statement from the heart failure association of the European society of cardiology, heart failure society of America and Japanese Heart Failure Society. J Card Fail 29(5):787–804. https://doi.org/10.1016/j.cardfail.2023.02.009CrossRefPubMed

15.

Ibrahim NE, Burnett JC Jr, Butler J et al (2020) Natriuretic peptides as inclusion criteria in clinical trials: a JACC: heart failure position paper. JACC Heart Fail 8(5):347–358. https://doi.org/10.1016/j.jchf.2019.12.010CrossRefPubMed

16.

Kammer M, Heinzel A, Willency JA et al (2019) Integrative analysis of prognostic biomarkers derived from multiomics panels helps discrimination of chronic kidney disease trajectories in people with type 2 diabetes. Kidney Int 96(6):1381–1388. https://doi.org/10.1016/j.kint.2019.07.025CrossRefPubMed

17.

Chan JCN, Lim LL, Luk AOY et al (2019) From Hong Kong diabetes register to JADE program to RAMP-DM for data-driven actions. Diabetes care 42(11):2022–2031. https://doi.org/10.2337/dci19-0003CrossRefPubMed

18.

Jiang G, Luk AO, Tam CHT et al (2020) Obesity, clinical, and genetic predictors for glycemic progression in Chinese patients with type 2 diabetes: a cohort study using the Hong Kong Diabetes Register and Hong Kong Diabetes Biobank. PLoS Med 17(7):e1003209. https://doi.org/10.1371/journal.pmed.1003209CrossRefPubMedPubMedCentral

19.

Jiang G, Luk AO, Tam CHT et al (2022) Clinical predictors and long-term impact of acute kidney injury on progression of diabetic kidney disease in Chinese patients with type 2 diabetes. Diabetes 71(3):520–529. https://doi.org/10.2337/db21-0694CrossRefPubMedPubMedCentral

20.

Piwernetz K, Home PD, Snorgaard O, Antsiferov M, Staehr-Johansen K, Krans M (1993) Monitoring the targets of the St Vincent Declaration and the implementation of quality management in diabetes care: the DIABCARE initiative. The DIABCARE Monitoring Group of the St Vincent Declaration Steering Committee. Diabet Med 10(4):371–377. https://doi.org/10.1111/j.1464-5491.1993.tb00083.xCrossRefPubMed

21.

Levey AS, Stevens LA, Schmid CH et al (2009) A new equation to estimate glomerular filtration rate. Ann Intern Med 150(9):604–612. https://doi.org/10.7326/0003-4819-150-9-200905050-00006CrossRefPubMedPubMedCentral

22.

Huelsmann M, Neuhold S, Strunk G et al (2008) NT-proBNP has a high negative predictive value to rule-out short-term cardiovascular events in patients with diabetes mellitus. Eur Heart J 29(18):2259–2264. https://doi.org/10.1093/eurheartj/ehn334CrossRefPubMed

23.

McDonagh TA, Metra M, Adamo M et al (2021) 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J 42(36):3599–3726. https://doi.org/10.1093/eurheartj/ehab368CrossRefPubMed

24.

Aoki S, Yamagishi K, Kihara T et al (2023) Risk factors for pre-heart failure or symptomatic heart failure based on NT-proBNP. ESC Heart Fail 10(1):90–99. https://doi.org/10.1002/ehf2.14149CrossRefPubMed

25.

Yang X, Kong AP, So WY et al (2006) Effects of chronic hyperglycaemia on incident stroke in Hong Kong Chinese patients with type 2 diabetes. Diabetes Metab Res Rev 23(3):220–226. https://doi.org/10.1002/dmrr.675CrossRef

26.

Yang X, So WY, Kong AP et al (2008) Development and validation of a total coronary heart disease risk score in type 2 diabetes mellitus. Am J Cardiol 101(5):596–601. https://doi.org/10.1016/j.amjcard.2007.10.019CrossRefPubMed

27.

Yang XL, So WY, Kong AP et al (2006) End-stage renal disease risk equations for Hong Kong Chinese patients with type 2 diabetes: Hong Kong Diabetes Registry. Diabetologia 49(10):2299–2308. https://doi.org/10.1007/s00125-006-0376-3CrossRefPubMed

28.

Yang XL, So WY, Kong AP et al (2007) Modified end-stage renal disease risk score for Chinese type 2 diabetic patients—the Hong Kong Diabetes Registry. Diabetologia 50(6):1348–1350. https://doi.org/10.1007/s00125-007-0639-7CrossRefPubMed

29.

Hayes AJ, Leal J, Gray AM, Holman RR, Clarke PM (2013) UKPDS outcomes model 2: a new version of a model to simulate lifetime health outcomes of patients with type 2 diabetes mellitus using data from the 30 year United Kingdom Prospective Diabetes Study: UKPDS 82. Diabetologia 56(9):1925–1933. https://doi.org/10.1007/s00125-013-2940-yCrossRefPubMed

30.

Basu S, Sussman JB, Berkowitz SA et al (2018) Validation of Risk Equations for Complications of Type 2 Diabetes (RECODe) using individual participant data from diverse longitudinal cohorts in the U.S. Diabetes Care 41(3):586–595. https://doi.org/10.2337/dc17-2002CrossRefPubMed

31.

McDonagh TA, Metra M, Adamo M et al (2023) 2023 Focused update of the 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J 44(37):3627–3639. https://doi.org/10.1093/eurheartj/ehad195CrossRefPubMed

32.

Heidenreich PA, Bozkurt B, Aguilar D et al (2022) 2022 AHA/ACC/HFSA guideline for the management of heart failure: executive summary: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol 79(17):1757–1780. https://doi.org/10.1016/j.jacc.2021.12.011CrossRefPubMed

33.

Januzzi JL Jr, Xu J, Li J et al (2020) Effects of canagliflozin on amino-terminal pro-B-type natriuretic peptide: implications for cardiovascular risk reduction. J Am Coll Cardiol 76(18):2076–2085. https://doi.org/10.1016/j.jacc.2020.09.004CrossRefPubMed

34.

Natriuretic Peptides Studies Collaboration, Willeit P, Kaptoge S et al (2016) Natriuretic peptides and integrated risk assessment for cardiovascular disease: an individual-participant-data meta-analysis. Lancet Diabetes Endocrinol 4(10):840–849. https://doi.org/10.1016/S2213-8587(16)30196-6CrossRefPubMedPubMedCentral

35.

Zelniker TA, Morrow DA, Mosenzon O et al (2021) Relationship between baseline cardiac biomarkers and cardiovascular death or hospitalization for heart failure with and without sodium-glucose co-transporter 2 inhibitor therapy in DECLARE-TIMI 58. Eur J Heart Fail 23(6):1026–1036. https://doi.org/10.1002/ejhf.2073CrossRefPubMed

36.

Malachias MVB, Jhund PS, Claggett BL et al (2020) NT-proBNP by itself predicts death and cardiovascular events in high-risk patients with type 2 diabetes mellitus. J Am Heart Assoc 9(19):e017462. https://doi.org/10.1161/JAHA.120.017462CrossRefPubMedPubMedCentral

37.

Chang KW, Hsu JC, Toomu A, Fox S, Maisel AS (2017) Clinical applications of biomarkers in atrial fibrillation. Am J Med 130(12):1351–1357. https://doi.org/10.1016/j.amjmed.2017.08.003CrossRefPubMed

38.

Patton KK, Ellinor PT, Heckbert SR et al (2009) N-terminal pro-B-type natriuretic peptide is a major predictor of the development of atrial fibrillation: the Cardiovascular Health Study. Circulation 120(18):1768–1774. https://doi.org/10.1161/CIRCULATIONAHA.109.873265CrossRefPubMedPubMedCentral

39.

Staerk L, Preis SR, Lin H et al (2020) Protein biomarkers and risk of atrial fibrillation: the FHS. Circ Arrhythm Electrophysiol 13(2):e007607. https://doi.org/10.1161/CIRCEP.119.007607CrossRefPubMedPubMedCentral

40.

Werhahn SM, Becker C, Mende M et al (2022) NT-proBNP as a marker for atrial fibrillation and heart failure in four observational outpatient trials. ESC Heart Fail 9(1):100–109. https://doi.org/10.1002/ehf2.13703CrossRefPubMed

41.

Desai AS, Toto R, Jarolim P et al (2011) Association between cardiac biomarkers and the development of ESRD in patients with type 2 diabetes mellitus, anemia, and CKD. Am J Kidney Dis 58(5):717–728. https://doi.org/10.1053/j.ajkd.2011.05.020CrossRefPubMed

42.

Levey AS, Gansevoort RT, Coresh J et al (2020) Change in albuminuria and GFR as end points for clinical trials in early stages of CKD: a scientific workshop sponsored by the national kidney foundation in collaboration with the US Food and Drug Administration and European Medicines Agency. Am J Kidney Dis 75(1):84–104. https://doi.org/10.1053/j.ajkd.2019.06.009CrossRefPubMed

43.

Jin Q, Lau ESH, Luk AO et al (2022) High-density lipoprotein subclasses and cardiovascular disease and mortality in type 2 diabetes: analysis from the Hong Kong Diabetes Biobank. Cardiovasc Diabetol 21(1):293. https://doi.org/10.1186/s12933-022-01726-yCrossRefPubMedPubMedCentral

44.

Jin Q, Lau ESH, Luk AO et al (2024) Circulating metabolomic markers linking diabetic kidney disease and incident cardiovascular disease in type 2 diabetes: analyses from the Hong Kong Diabetes Biobank. Diabetologia 67(5):837–849. https://doi.org/10.1007/s00125-024-06108-5CrossRefPubMedPubMedCentral

45.

Fadini GP, Bonora BM, Albiero M, Zaninotto M, Plebani M, Avogaro A (2017) DPP-4 inhibition has no acute effect on BNP and its N-terminal pro-hormone measured by commercial immune-assays. A randomized cross-over trial in patients with type 2 diabetes. Cardiovasc Diabetol 16(1):22. https://doi.org/10.1186/s12933-017-0507-9CrossRefPubMedPubMedCentral

46.

Yang X, Ma RC, So WY et al (2008) Development and validation of a risk score for hospitalization for heart failure in patients with type 2 diabetes mellitus. Cardiovasc Diabetol 7:9. https://doi.org/10.1186/1475-2840-7-9CrossRefPubMedPubMedCentral

Title: NT-proBNP improves prediction of cardiorenal complications in type 2 diabetes: the Hong Kong Diabetes Biobank
Authors: Ronald C. W. Ma
Claudia H. T. Tam
Yong Hou
Eric S. H. Lau
Risa Ozaki
Juliana N. M. Lui
Elaine Chow
Alice P. S. Kong
Chuiguo Huang
Alex C. W. Ng
Erik G. Fung
Andrea O. Y. Luk
Wing Yee So
Cadmon K. P. Lim
Juliana C. N. Chan
for the Hong Kong Diabetes Biobank Study Group
Publication date: 07-11-2024
Publisher: Springer Berlin Heidelberg
Keywords: Type 2 Diabetes
Heart Failure
Biomarkers
Atrial Fibrillation
Published in: Diabetologia
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI: https://doi.org/10.1007/s00125-024-06299-x

Keynote series | Spotlight on menopause

Menopause
Video Series

Menopause can have a significant impact on the body, with effects ranging beyond the endocrine and reproductive systems. Learn about the broader systemic effects of menopause, so you can help patients in your clinics through the transition.

Launching: Thursday 12th December 2024

Prof. Martha Hickey

Dr. Claudia Barth

Dr. Samar El Khoudary

Developed by: Springer Medicine

Keynote webinar | Spotlight on adolescent vaping

Live
Webinar | 29-01-2025 | 18:00 (CET)

Growing numbers of young people are using e-cigarettes, despite warnings of respiratory effects and addiction. How can doctors tackle the epidemic, and what health effects should you prepare to manage in your clinics?

Watch it live: Wednesday 29th January, 18:00-19:30 CET

Prof. Ann McNeill

Dr. Debbie Robson

Benji Horwell

Developed by: Springer Medicine

Join the webinar

Keynote webinar | Spotlight on modern management of frailty

Frailty in Geriatric Patients
On-demand webinar

Frailty has a significant impact on health and wellbeing, especially in older adults. Our experts explain the factors that contribute to the development of frailty and how you can manage the condition and reduce the risk of disability, dependency, and mortality in your patients.

Prof. Alfonso Cruz-Jentoft

Prof. Barbara C. van Munster

Prof. Mirko Petrovic

Developed by: Springer Medicine

Watch now

A quick guide to ECGs

Electrocardiography
Training Course

Improve your ECG interpretation skills with this comprehensive, rapid, interactive course. Expert advice provides detailed feedback as you work through 50 ECGs covering the most common cardiac presentations to ensure your practice stays up to date.

PD Dr. Carsten W. Israel

Developed by: Springer Medizin

Start the cases

At a glance: The STEP trials

Obesity
Clinical Trial Summary

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Keynote series | Spotlight on menopause

Springer Medicine

Abstract

Aims/hypothesis

Methods

Results

Conclusions/interpretation

Graphical Abstract

Please log in to get access to this content

Keynote series | Spotlight on menopause

Keynote webinar | Spotlight on adolescent vaping

Keynote webinar | Spotlight on modern management of frailty

A quick guide to ECGs

At a glance: The STEP trials