Beta-adrenergic reactivity of erythrocyte membranes in various phenotypes of uncontrolled hypertension

Aim. To assess the functional state of the sympathetic nervous system according to β-adrenergic reactivity of erythrocyte membranes (EM) in patients with refractory (rfHTN) and resistant hypertension (rHTN) in relation to target organ damage.

Material and methods. The cross-sectional comparative study included 78 patients with uncontrolled hypertension (mean age, 57,4±9,3 years (33 men)) with 24-hour blood pressure (BP) (systolic/diastolic) of 160,0±18,8/88,1±17,3 mm Hg. Thirty-nine (50%) patients had type 2 diabetes (T2D). At baseline, patients were divided into 2 groups depending on the phenotype of uncontrolled hypertension. The first group consisted of patients with rfHTN (n=26 (33,3%)), the second — with rHTN (uncontrolled BP with 3-4 agent therapy) (n=52 (66,7%)). In all patients, office and mean 24-hour blood pressure, EM β-adrenergic reactivity and target organ damage were assessed.

Results. The compared groups did not differ in sex and age composition, prevalence of T2D and basic clinical data. However, despite comparable levels of office and mean 24-hour blood pressure, the incidence of left ventricular (LV) hypertrophy according to echocardiography in rfHTN was significantly higher than in rHTN (96,2% vs 76,9%, p=0,027, respectively). An increase in EM β-adrenergic reactivity (>20 conventional units) was documented in 87,1% of patients in the general group. Moreover, the mean EM β-adrenergic reactivity in the rfHTN group was significantly higher than in the rHTN group (51,5±18,7 vs 39,3±18,2, p=0,008). According to ROC analysis, the threshold value of EM β-adrenergic reactivity corresponding to rfHTN was ≥44,8 conventional units (sensitivity — 69,2%, specificity — 64,5%, area under the ROC curve — 0,687). The mean EM β-adrenergic reactivity in the rfHTN group did not have a direct relationship with the LV mass index, but correlated with increased pulse pressure.

Conclusion. RfHTN is associated with higher EM β-adrenergic reactivity values than in patients with rHTN, which may indirectly confirm more pronounced sympathetic activity and explain the higher prevalence of LVH, realized through an increase in vascular stiffness and load on the LV.

1. Mann SJ. Neurogenic hypertension: pathophysiology, diagnosis and management. Clin Auton Res. 2018;28(4):363-74. doi:10.1007/s10286-018-0541-z.

2. Matanes F, Khan MB, Siddiqui M, et al. An update on refractory hypertension. Curr Hypertens Rep. 2022;24(7):225-34. doi:10.1007/s11906-022-01185-6.

3. Bacan G, Ribeiro-Silva A, Oliveira VAS, et al. Refractory hypertension: a narrative systematic review with emphasis on prognosis. Curr Hypertens Rep. 2022;24(4):95-106. doi:10.1007/s11906-022-01165-w.

4. Denisova AR, Solntseva TD, Zarmanbetova AS, et al. The incidence of cardiovascular and cerebrovascular complications in patients with uncontrolled hypertension. Terapevticheskii Arkhiv (Ter. Arkh.). 2022;94(1):94-9. (In Russ.). doi:10.26442/00403660.2022.01.201395.

5. Dudenbostel T, Acelajado MC, Pisoni R, et al. Refractory Hypertension: Evidence of heightened sympathetic activity as a cause of antihypertensive treatment failure. Hypertension. 2015;66(1):126-33. doi:10.1161/HYPERTENSIONAHA.115.05449.

6. Stryuk RI, Dlusskaya IG. Adrenoreactivity and cardiovascular system. M: Medicine, 2003. p. 160. (In Russ.) ISBN: 5-225-04337-2.

7. Seravalle G, Grassi G. Sympathetic nervous system and hypertension: new evidences. Auton Neurosci. 2022;238:102954. doi:10.1016/j.autneu.2022.102954.

8. Vorobyova DA, Rebrova TYu, Afanasyev SA, et al. Comparative analysis of adrenergic reactivity of erythrocytes in patients with myocardial infarction depending on the severity of coronary obstruction. Russian Journal of Cardiology. 2020;25(5):3735. (In Russ.). doi:10.15829/1560-4071-2020-3735.

9. Rebrova TYu, Muslimova EF, Alexandrenko VA, et al. Dynamics of adreneractivity after transfer of myocardial infarction: annual observation. Ter Arkh. 2021;93(1):44-8. (In Russ.). doi:10.26442/00403660.2021.01.200592.

10. Garganeeva AA, Aleksandrenko VA, Kuzheleva EA, et al. Beta-adrenergic reactivity of erythrocytes and the progression of heart failure in patients after myocardial infarction. Russian Journal of Cardiology. 2020;25(1):3407. (In Russ.). doi:10.15829/1560-4071-2020-1-3407.

11. Aleksandrenko VA, Rebrova TYu, Afanasiev SA, et al. Association of Adrenoreactivity with the Stage of Chronic Heart Failure in Patients with Previous Myocardial Infarction. The Siberian Medical Journal. 2019;34(2):79-83. (In Russ.). doi:10.29001/20738552-2019-34-2-79-83.

12. Zyubanova IV, Falkovskaya AYu, Mordovin VF, et al. Erythrocyte membranes beta-adrenoreactivity changes after renal denervation in patients with resistant hypertension, relationship with antihypertensive and cardioprotective intervention efficacy. Kardiologiia. 2021;61(8):32-9. (In Russ.). doi:10.18087/cardio.2021.8.n1556.

13. Falkovskaya AYu, Mordovin VF, Pekarskiy SE, et al. Refractory and resistant hypertension in patients with type 2 diabetes mellitus: differences in metabolic profile and endothelial function. Terapevticheskii Arkhiv (Ter. Arkh.). 2021;93(1):49-58. (In Russ.. doi:10.26442/00403660.2021.01.200593.

14. Orekhov AYu, Karazhanova LK. The role of the sympathetic nervous system in resistant hypertension: pathophysiological and clinical aspects. "Arterial'naya Gipertenziya" ("Arterial Hypertension"). 2022;28(4):348-56. (In Russ.). doi:10.18705/1607-419X-2022-28-4-348-356.

15. Moyá-Amengual A, Ruiz-García A, Pallarés-Carratalá V, et al. Elevated pulse pressure and cardiovascular risk associated in Spanish population attended in primary care:IBERICAN study. Front Cardiovasc Med. 2023;10:1090458. doi:10.3389/fcvm.2023.1090458.