The level of N-terminal pro-brain natriuretic peptide depending on vascular wall condition and bone mass in postmenopausal women

Aim. To assess the relationship of serum N-terminal pro-brain natriuretic peptide (NT-proBNP) levels with vascular wall condition and bone mineral density (BMD) in postmenopausal women.

Material and methods. The cross-sectional study included 107 outpatients aged 45-82 years who signed informed consent. The inclusion criterion was a menopause during ≥1 year. The level of serum NT-proBNP was determined by electrochemiluminescence. BMD was assessed by dual energy x-ray absorptiometry. Intima-media thickness (IMT), the presence and number of atherosclerotic plaques were evaluated using carotid duplex scanning. Pulse wave velocity (PWV) and augmentation index were estimated by applanation tonometry. To assess 10-year cardiovascular risk, the SCORE high-risk charts were used. Using the Russian model of FRAX® score, 10-year fracture risk was assessed.

Results. NT-proBNP level in women with postmenopause >10 years was significantly higher than in those with postmenopause <5 years — 98,7 vs 56,3 pg/ml (p<0,001), but there was no independent relationship according to the regression analysis. According to multivariate regression analysis adjusted for age, menopause duration, systolic blood pressure, hypercholesterolemia, smoking, elevated C-reactive protein and interleukin-6 levels, there were independent relationship between the following parameters: NT-proBNP and IMT (β=2,38, p<0,03), NT-proBNP and PWV (β=1,76, p<0,001). NT-proBNP level in patients with osteoporosis was significantly higher than in women with normal bone mass (p<0,01). A negative correlation was observed between NT-proBNP and BMD of the proximal femur (r=-0,26, p<0,05), while the relationship between BMD of the lumbar vertebrae (L1-L4) and NT-proBNP did not reach significance. In multivariate regression analysis, this relationship has not been confirmed. A positive correlation was obtained between cardiovascular risk (SCORE) and NT-proBNP levels (r=0,28, p<0,001). NT-proBNP levels did not differ in women with a high and low 10-year risk of both major osteoporotic fractures and femoral fractures.

Conclusion. An independent relationship of NT-proBNP with vascular stiffness and preclinical atherosclerosis was demonstrated: IMT and PWV. This indicates the participation of NT-proBNP in the atherosclerosis development. The association of elevated NT-proBNP levels with osteoporosis is significant, but not independent, and is apparently related to other factors.

1. Den Uyl D, Nurmohamed MT, van TuylLilian HD, et al. (Sub)clinical cardiovascular disease is associated with increased bone loss and fracture risk; a systematic review of the association between cardiovascular disease and osteoporosis. Arthritis Res Ther. 2011;13(1): R5. doi:10.1186/ar3224.

2. Fohtung RB, Brown DL, Koh WJH, et al. Bone mineral density and risk of heart failure in older adults: the cardiovascular health study. J Am Heart Assoc. 2017;6:e004344. doi:10.1161/JAHA.116.004344.

3. Mangiafico RA, Alagona C, Pennisi P. Increased augmentation index and central aortic blood pressure in osteoporotic postmenopausal women. Osteoporos Int. 2008;19:49-56. doi:10.1007/s00198-007-0438-5.

4. Varri M, Tuomainen TP, Honkanen R, et al. Carotid intima-media thickness and calcification in relation to bone mineral density in postmenopausal women-the ostpre-bba study. Maturitas. 2014;78(4):304-9. doi:10.1016/j.maturitas.2014.05.017.

5. Alikhanova NA, Skripnikova IA, Tkacheva ON, et al. Association of vessel stiffness parameters and subclinical atherosclerosis and mass of bone tissue in postmenopausal women. Cardiovascular Therapy and Prevention. 2016;15(2):51-6. (In Russ.) doi:10.15829/1728-8800-2016-2-51-56.

6. Larina VR, Raspopova TN. bone Mineral density and bone metabolism in chronic heart failure. Kardiologiia. 2016;56(7):17-24. (In Russ.) doi:10.18565/cardio.2016.7.13-24.

7. Mel`nichenko GA, Belaya ZhE, Rozhinskaya LYa, et al. Russian federal clinical guidelines on the diagnostics, treatment, and prevention of osteoporosis. Problems of Endocrinology. 2017;63(6):392-426. (In Russ.) doi:10.14341/probl2017636392-426.

8. Boytsov SA, Pogosova NV, Bubnova MG, et al. National guidelines. Russ J Cardiol. 2018;23(6):7-122. (In Russ.) doi:10.15829/1560-4071-2018-6-7-122.

9. Makovey J, Macara M, Chen JS, et al. Highosteoporotic fracture risk and CVD risk co-exist in postmenopausal women. Bone. 2013;52:120-5. doi:10.1016/j.bone.2012.09.02.

10. Myagkova MA, Skripnikova IA, Kosmatova OV, et al. Association of absolute risk of osteoporotic fractures (FRAX®) and total cardiovascular risk (SCORE) among the urban population of the Russian Federation. Cardiovascular Therapy and Prevention. 2019;18(5):108-16. (In Russ.) doi:10.15829/1728-8800-2019-5-108-116.

11. Kawińska-Hamala A, Kawiński A, Stanek K, et al. Correlations between 10-year risk of death from cardiovascular diseases and 10-year osteoporotic fracture risk in postmenopausal women. Endokrynologia Polska. 2017;68 (4):390-7. doi:10.5603/EP.a2017.0030.

12. Berger R, Moertl D, Peter S, et al. N-terminal ProB-Type Natriuretic Peptide-Guided, Intensive Patient Management in Addition to Multidisciplinary Care in Chronic Heart Failure. J Am Coll Cardiol. 2010;55:645-54. doi:10.1210/endo.141.12.7847.

13. Redfield M, Rodeheffer R, Jacobsen S, et al. Plasma brain natriuretic peptide concentration impact of age and gender. J Am Coll Cardiol. 2002;40:976-82. doi:10.1016/s0735-1097(02)02059-4.

14. Di Angelantonio E, Chowdhury R, Sarwar N, et al. B-type natriuretic peptides and cardiovascular risk: systematic review and meta-analysis of 40 prospective studies. Circulation. 2009;120:2177-87. doi:10.1161/circulationaha.109.884866.

15. Gan L, Feng C, Liu C, et al. Association between serum N-terminalpro B-type natriuretic peptide levels and characteristics of coronary atherosclerotic plaque detected by coronary computedtomography angiography. Exp Ther Med. 2016;12(2):667-75. doi:10.3892/etm.2016.3371.

16. Odden MC, Shlipak MG, Whitson HE, et al. Risk factors for cardiovascular diseases across the spectrum of older age: theCardiovascular Health Study. Atherosclerosis. 2014;237(1):336-42. doi:10.1016/j.atherosclerosis.2014.09.012.

17. Beleigoli AM, Diniz MF, Ribeiro AL. Natriuretic peptides:linking heart and adipose tissue in obesity and related conditions: asystematic review. Obes Rev. 2009;10:617- 626. doi:10.1111/j.1467-789X.2009.00624.x.

18. Loncar G, Fülster S, von Haehling S, et al. Metabolism andthe heart: An overview of muscle, fat, and bone metabolism in heartfailure. Int J Cardiol. 2013;162:77. doi:10.1016/j.ijcard.2011.09.079.

19. Mareev VYu, Fomin IV, Ageev FT, et al. Russian Heart Failure Society, Russian Society of Cardiology. Russian Scientific Medical Society of Internal Medicine Guidelines for Heart failure: chronic (CHF) and acute decompensated (ADHF). Diagnosis, prevention and treatment. Kardiologiia. 2017;58:8-158. (In Russ.) doi:10.18087/cardio.2475.

20. Passino C, Polleti R, Fontana M, et al. Clinical relevance of non-cardiac determinants of natriuretic peptide levels. Clin Chem Lab Med. 2008;46:1515-23. doi:10.1515/CCLM.2008.293.

21. Zhou W, Ni Z, Yu Z, et al. Brain natriuretic peptide is related to carotid plaques and predicts atherosclerosis inpredialysis patients with chronic kidney disease. Eur J Intern Med. 2012;23:539-44. doi:10.1016/j.ejim.2012.06.001.

22. Liu S, Kim ED, Wu A, et al. Central and peripheral pulse wave velocity and subclinical myocardial stress and damage in older adults. PLoS One. 2019;14(2):e0212892. doi:10.1371/journal.pone.0212892. eCollection 2019.

23. Lee MC, Lee CL, Shih GJ, et al. N-terminal pro B-type peptide is inversely related to bone mineral density in renal transplant recipients. Transplantation Proceedings. 2014;46:3443-47. doi:10.1016/j.transproceed.2014.06.077.

24. Barasch E, Gottdiener JS, Aurigemma G, et al. Association Between Elevated Fibrosis Markers and Heart Failure in the Elderly. The Cardiovascular Health Study. Circ Heart Fail. 2009;2:303-10. doi:10.1161/CIRCHEARTFAILURE.108.828343.

25. Ulrich S, Hersberger M, Fischler M, et al. Bone Mineral Density and Secondary Hyperparathyroidism in Pulmonary Hypertension. The Open Respiratory Medicine J. 2009;3:53-60. doi:10.2174/1874306400903010053.