Significance of the N-terminal pro-B-type natriuretic peptide in the development of left ventricular diastolic dysfunction in type 2 diabetes mellitus

   Introduction. Left ventricular diastolic dysfunction (LV DD) is associated with the development of chronic heart failure (CHF) with preserved ejection fraction. This CHF phenotype is most common in patients with type 2 diabetes mellitus (T2DM). It is relevant to study the relationship between LV DD in patients with T2DM and the level of N-terminal pro-B-type natriuretic peptide (NT-proBNP), as a CHF biomarker, and other clinical, laboratory and echocardiographic parameters.
   Aim. To determine the signifi cance of NT-proBNP and other factors in the development of LV DD in T2DM in the long-term follow-up period.
   Materials and methods. The study included 94 patients with T2DM aged 40 to 65 years (65 % women). All patients had arterial hypertension (AH), obese or overweight and had no signs of NYHA class III–IV CHF, LV ejection fraction (EF) < 50 %. 37 patients had stable coronary artery disease (SCAD). Patients underwent clinical and laboratory examination, echocardiography. The concentration of NT-proBNP was determined. After 8.8 ± 0.72 years, 41 patients with T2DM were examined again with an assessment of clinical, biochemical and echocardiographic parameters. At baseline the 2009 National Guidelines of the Society of Cardiology of the Russian Federation and the Society of Heart Failure Specialists for the diagnosis and treatment of CHF were used for the diagnosis of LV DD. After 8.8 ± 0.72 years, the 2020 Clinical Guidelines of the Russian Society of Cardiology (RSC) for CHF were used for the diagnosis of LV DD. The search for factors that determine the presence of LV DD in the long-term period was carried out using logistic regression and ROC analysis.
   Results. At baseline LV DD was detected in 81.9 % of cases in patients with T2DM and correlated with the presence of SCAD and the duration of AH. T2DM patients with LV DD compared with patients without LV DD did not differ in the level of NT-proBNP (30.6 pg/ml [20; 83.4] vs 36.7 pg/ml [20; 71.1]), p = 0.7). After 8.8 ± 0.72 years, LV DD was detected in 51.2 % of patients with T2DM according to the 2020 Clinical Guidelines of the RSC. Patients with T2DM were divided into 2 groups: with LV DD (group 1) and without LV DD (group 2). Patients of the first and second groups differed in duration of diabetes (20 years [16; 25] vs 17.5 years [14.5; 20.5], р = 0.04), body mass index (BMI) (33.9 kg/m² [31.2; 37.4] vs 32.2 kg/m² [27.4; 34.7], р = 0.03), left ventricular mass index (LVMI) (94.8 g/m 2 [82.5; 107] vs 73.9 g/m² [71; 82.7], p < 0.01) and were comparable in terms of carbohydrate, lipid metabolism, and kidney function. Compared to the second group, the first group had the higher baseline level of NT-proBNP (47.3 pg/ml [23.4; 111] vs 20 pg/ml [20; 20.3], p < 0.01), higher baseline BMI (34.6 kg/m² [30; 38] vs 31.2 kg/m² [29.6; 33.7], р = 0.04) and higher baseline LVMI (101.1 ± 1 g/m² vs 86.3 ± 14.1 g/m² , р = 0.02). The logistic regression revealed that in patients with T2DM the presence of LV DD in the long-term period is associated with the level of NT-proBNP (p = 0.03), baseline BMI (p = 0.04), baseline LVMI (p = 0.01). The baseline level of NT-proBNP > 31.2 pg/ml showed a sensitivity of 66.7 % and a specificity of 100 % for the presence of LV DD in patients with T2DM after 8.8 ± 0.72 years of follow-up.
   Conclusion. In the long-term follow-up period the presence of LV DD in patients with type 2 diabetes mellitus is associated with the increased baseline level of NT-proBNP, especially in combination with the increased baseline LVMI and BMI values, while the level of NT-proBNP > 31.2 pg/ml can be considered as a prognostic marker of LV DD in patients with T2DM after 8.8 ± 0.72 years of follow-up with a sensitivity of 66.7 % and a specifi city of 100 %.

1. Dedov I. I., Shestakova M. V., Vikulova O. K., Zheleznyakova A. V., Isakov M. A. Epidemiological characteristics of diabetes mellitus in the Russian Federation: clinical and statistical analysis according to the Federal Diabetes Register data of 01. 01. 2021. Diabetes Mellitus. 2021; 24 (3): 204-221. DOI: 10.14341/DM12759. (In Russ.)

2. 2020 Clinical practice guidelines for chronic heart failure. Russian Journal of Cardiology. 2020; 25 (11): 311-374. DOI: 10.15829/1560-4071-2020-4083. (In Russ.)

3. Nishimura R. A., Borlaug B. A. Diastology for the clinician // J. Cardiol. 2019; 73 (6): 445-452. DOI: 10.1016/j.jjcc.2019.03.002.

4. Nagueh S. F. Left ventricular diastolic function: understanding pathophysiology, diagnosis, and prognosis with echocardiography // JACC Cardiovasc. Imaging. 2020; 13 (2): 228-244. DOI: 10.1016/j.jcmg.2018.10.038.

5. Nagueh S. F., Smiseth O. A., Appleton C. P. et al. Recommendations for the evaluation of left ventricular diastolic function by echocardiography: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging // J. Am. Soc. Echocardiogr. 2016; 29 (4): 277-314. DOI: 10.1016/j.echo.2016.01.011.

6. Echouff o-Tcheugui J. B., Erqou S., Butler J., Yancy C. W., Fonarow G. C. Assessing the risk of progression from asymptomatic left ventricular dysfunction to overt heart failure: a systematic overview and meta-analysis // JACC Heart Fail. 2016; 4 (4): 237-248. DOI: 10.1016/j.jchf.2015.09.015.

7. Ladeiras-Lopes R., Araújo M., Sampaio F., Leite-Moreira A., Fontes-Carvalho F. The impact of diastolic dysfunction as a predictor of cardiovascular events: A systematic review and meta-analysis // Rev. Port. Cardiol. 2019; 38 (11): 789-804. DOI: 10.1016/j.repc.2019.03.007.

8. Ravassa S., Kuznetsova T., Varo N. et al. Biomarkers of cardiomyocyte injury and stress identify left atrial and left ventricular remodelling and dysfunction: а population-based study // Int. J. Cardiol. 2015; 185: 177-185. DOI: 10.1016/j.ijcard.2015.03.046.

9. Национальные рекомендации ВНОК и ОССН по диагностике и лечению ХСН (третий пересмотр) (утверждены конференцией ОССН 15 декабря 2009 года) // Сердечная недостаточность. – 2010. – 11 (1) (57): 3-62.

10. Lang R. M., Badano L. P., Mor-Avi V. et al. Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging // J. Am. Soc. Echocardiogr. 2015; 28 (1): 1-39. DOI: 10.1016/j.echo.2014.10.003.

11. Bondar I. A., Demin A. A., Shabelnikova O. Yu. Morphological and functional parameters of the heart and vessels in patients with type 2 diabetes mellitus and cardiovascular autonomic neuropathy. Diabetes Mellitus. 2014; 2: 41-46. DOI: 10.14341/DM2014241-46. (In Russ.)

12. Sumin A. N., Osokina A. V., Shcheglova A. V., Frolova S. A., Barbarash O. L. Assessment of cardio-ankle vascular index in patients with coronary artery disease with a different type of diastolic dysfunction of the left ventricle. Complex Issues of Cardiovascular Diseases. 2016; 2: 51-58. DOI: 10.17802/2306-1278-2016-2-51-58. (In Russ.)

13. Almeida J. G., Fontes-Carvalho R., Sampaio F. et al. Impact of the 2016 ASE/EACVI recommendations on the prevalence of diastolic dysfunction in the general population // Eur. Heart J. Cardiovasc. Imaging. 2018; 19 (4): 380-386. DOI: 10.1093/ehjci/jex252.

14. Wan S. H., Pumerantz A. S., Dong F., Ochoa C., Chen H. H. Comparing the infl uence of 2009 versus 2016 ASE/EACVI diastolic function guidelines on the prevalence and echocardiographic characteristics of preclinical diastolic dysfunction (stage B heart failure) in a Hispanic population with type 2 diabetes mellitus // J. Diabetes Complications. 2019; 33 (8): 579-584. DOI: 10.1016/j.jdiacomp.2019.04.015.

15. Agrawal V., Byrd 3rd B. F., Brittain E. L. Echocardio graphic evaluation of diastolic function in the setting of pulmonary hypertension // Pulm. Circ. 2019; 9 (1): 2045894019826043. DOI: 10.1177/2045894019826043.

16. Choi H. I., Lee M. Y., Oh B. K. et al. Effects of age, sex, and obesity on N-terminal pro B-type natriuretic peptide concentrations in the general population // Circ. J. 2021; 85 (5): 647-654. DOI: 10.1253/circj.CJ-20-1104.

17. Buckley L. F., Canada J. M., Del Buono M. G. et al. Low NT-proBNP levels in overweight and obese patients do not rule out a diagnosis of heart failure with preserved ejection fraction // ESC Heart Fail. 2018; 5 (2): 372-378. DOI: 10.1002/ehf2.12235.

18. Baldassarre S., Fragapani S., Panero A. et al. NTproBNP in insulin-resistance mediated conditions: overweight / obesity, metabolic syndrome and diabetes. The population-based Casale Monferrato Study // Cardiovasc. Diabetol. 2017; 16 (1): 119. DOI: 10.1186/s12933-017-0601-z.

19. Mueller C., McDonald K., de Boer R. A. et al. Heart Failure Association of the European Society of Cardiology practical guidance on the use of natriuretic peptide concentrations // Eur. J. Heart Fail. 2019; 21 (6): 715-731. DOI: 10.1002/ejhf.1494.

20. Mocan M., Anton F., Suciu Ș. et al. Multimarker assessment of diastolic dysfunction in metabolic syndrome patients // Metab. Syndr. Relat. Disord. 2017; 15 (10): 507-514. DOI: 10.1089/met.2017.0060.

21. Chau K., Girerd N., Magnusson M. et al. Obesity and metabolic features associated with long-term developing diastolic dysfunction in an initially healthy population-based cohort // Clin. Res. Cardiol. 2018; 107 (10): 887-896. DOI: 10.1007/s00392-018-1259-6.

22. Nah E. H., Kim S. Y., Cho S., Kim S., Cho H. I. Plasma NT-proBNP levels associated with cardiac structural abnormalities in asymptomatic health examinees with preserved ejection fraction: a retrospective cross-sectional study // BMJ Open. 2019; 9 (4): e026030. DOI: 10.1136/bmjopen-2018-026030.

23. Remmelzwaal S., van Ballegooijen A. J., Schoonmade L. J. et al. Natriuretic peptides for the detection of diastolic dysfunction and heart failure with preserved ejection fraction – a systematic review and meta-analysis // BMC Med. 2020; 18 (1): 290. DOI: 10.1186/s12916-020-01764-x.