Endothelium-mediated vasodilation: associations with cardiometabolic diseases and their risk factors in aging

Aim. To evaluate the association of flow-mediated vasodilation (FMD) with cardiometabolic diseases (CMDs) and their risk factors (RF) in old age.

Material and methods. The study was conducted in the Russian population cohort of the HAPIEE project (Novosibirsk, 2015-2018). Endothelial function was assessed in a random subsample (788 men and women aged 55-84 years) using ultrasound measurements of the brachial artery FMD. Endothelial dysfunction (ED) was recorded with FMD <10%. Cardiovascular diseases (CVD) and risk factors were assessed using standard epidemiological methods.

Results. The incidence of hypertension (HTN) was 78,8% (the same in men and women), major CVDs — 21,7% and 17,1%, type 2 diabetes (T2D) — 18,7% and 19,1% in men and women, respectively. The mean FMD values were 2,7% (SD 7,32) and 3,2% (7,19), while the prevalence of ED was 88,2% and 85,8% in men and women, respectively, and did not differ significantly by sex. Men with ED had higher levels of blood triglycerides (125,1 (71,23) vs 102,7 (45,79) mg/dl; p=0,033), waist/hip circumference indices (0,94 (0,050) vs 0,92 (0,076); p=0,009) and body weight (27,7 (45,79) vs 26,5 (4,36) kg/m²; p=0,077). In women, a tendency towards an association of ED with smoking was revealed (p=0,067). There were no associations of ED with HTN, T2D and CVD in men and women.

Conclusion. The PMD test demonstrated a high incidence of ED in a population sample of 55-84 years old. ED is associated with metabolic risk factors in men and smoking in women. No associations of PMD with CMDs were found, presumably due to the high incidence of ED and cumulative disease in the elderly. Modification of metabolic risk factors and smoking cessation are relevant at any age to prevent the progression of ED.

1. Ryliškytė L, Navickas R, Šerpytis P, et al. Association of aortic stiffness, carotid intima-media thickness and endothelial function with cardiovascular events in metabolic syndrome subjects. Blood Press. 2019;28(2):131-8. doi:10.1080/08037051.2019.1569461.

2. Soboleva GN, Fedulov VK, Karpov YuA. Arterial endothelial dysfunction and its role for prognosis assessment in cardiovascular patients. Cardiovascular Therapy and Prevention. 2010;9(2):69-73. (In Russ.)

3. Alexander Y, Osto E, Schmidt-Trucksäss A, et al. Endothelial function in cardiovascular medicine: a consensus paper of the European Society of Cardiology Working Groups on Atherosclerosis and Vascular Biology, Aorta and Peripheral Vascular Diseases, Coronary Pathophysiology and Microcirculation, and Thrombosis. Cardiovasc Res. 2021;117(1):29-42. doi:10.1093/cvr/cvaa085.

4. Yanovskaya GR, Belov VV, Bolotov AA. Endothelial function in young men with essential hypertension. Russian Journal of Cardiology. 2004;(3):21-5. (In Russ.)

5. Thijssen DHJ, Bruno RM, van Mil ACCM, et al. Expert consensus and evidence-based recommendations for the assessment of flow-mediated dilation in humans. Eur Heart J. 2019;40(30):2534-47. doi:10.1093/eurheartj/ehz350.

6. Population-based assessment of endothelial dysfunction: prevalence, determinants, and association with cardiovascular diseases. In. Endothelial dysfunction, hypertension, atherosclerosis. Novosibirsk: Siberian Branch of the Russian Academy of Sciences. 2014:43-76. (In Russ.) ISBN: 978-5-7692-1382-3.

7. Yeboah J, Burke GL, Crouse JR, et al. Relationship between brachial flow-mediated dilation and carotid intima-media thickness in an elderly cohort: the Cardiovascular Health Study. Atherosclerosis. 2008;197(2):840-5. doi:10.1016/j.atherosclerosis.2007.07.032.

8. Benjamin EJ, Larson MG, Keyes MJ, et al. Clinical correlates and heritability of flow-mediated dilation in the community: the Framingham Heart Study. Circulation. 2004;109(5):613-9. doi:10.1161/01.CIR.0000112565.60887.1E.

9. Zhong Q, Nong Q, Mao B, et al. Association of Impaired Vascular Endothelial Function with Increased Cardiovascular Risk in Asymptomatic Adults. Biomed Res Int. 2018;2018:3104945. doi:10.1155/2018/3104945.

10. Fedulov VK, Soboleva GN, Rogoza AN, et al. Vascular wall structure and function in patients with CHD, AH, and their combination. Cardiovascular Therapy and Prevention. 2011;10(1):73-9. (In Russ.)

11. Troshina MS, Ryabikov AN, Palekhina YuYu, et al. Endothelial function and structural markers of atherosclerosis: relationship in old and senile age. Russian Journal of Cardiology. 2021;26(12):4614. (In Russ.) doi:10.15829/1560-4071-2021-4614.

12. Malyutina SK, Mazdorova EV, Shapkina MYu, et al. The Profile of Drug Treatment in Sub­jects Aged Over 50 Years With Hypertension in an Urban Russian Population. Kardiologiia. 2020;60(3):21-9. (In Russ.) doi:10.18087/cardio.2020.3.n948.

13. Samsamshariat SZA, Sakhaei F, Salehizadeh L, et al. Relationship between Resistin, Endothelin-1, and Flow-Mediated Dilation in Patient with and without Metabolic Syndrome. Adv Biomed Res. 2019;8:16. doi:10.4103/abr.abr_126_18.

14. Calder PC. Dietary factors and low grade inflammation in relation to overweight and obesity revisted. Br J Nutr. 2022;127(10):1-9. doi:10.1017/S0007114522000782.

15. Gallucci G, Tartarone A, Lerose R, et al. Cardiovascular risk of smoking and benefits of smoking cessation. J Thorac Dis. 2020;12(7):3866-76. doi:10.21037/jtd.2020.02.47.

16. Cui M, Cui R, Liu K, et al. Associations of Tobacco Smoking with Impaired Endothelial Function: The Circulatory Risk in Communities Study (CIRCS). J Atheroscler Thromb. 2018;25(9):836-45. doi:10.5551/jat.421.

17. Mogi M, Higashi Y, Bokuda K, et al. Annual reports on hypertension research 2020. Hypertens Res. 2022;45(1):15-31. doi:10.1038/s41440-021-00766-3.

18. Calderón-Gerstein WS, López-Peña A, Macha-Ramírez R, et al. Endothelial dysfunction assessment by flow-mediated dilation in a high-altitude population. Vasc Health Risk Manag. 2017;13:421-6. doi:10.2147/VHRM.S151886.