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Year : 2021  |  Volume : 6  |  Issue : 1  |  Page : 21-22

Initiating and secondary mechanisms of hypertension along the time course

Department of Cardiology, Beijing Tsinghua Changgung Hospital, Beijing, China

Date of Submission12-Jan-2021
Date of Acceptance01-Mar-2021
Date of Web Publication30-Mar-2021

Correspondence Address:
Zhi-Yi Ma
Department of Cardiology, Beijing Tsinghua Changgung Hospital
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/2470-7511.312598

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Due to the difference in drug treatment strategies between the “2020 International Society of Hypertension Global Hypertension Practice Guidelines” and the “Expert consensus on the management of hypertension in the young and middle-aged Chinese population” consensus, I made a hypothesis on hypertension mechanisms. The mechanisms behind hypertension differ between age groups. For instance, the sympathetic nervous system might play more important role young and middle-aged hypertensive patients. In this commentary, hypertension mechanisms were classified into initiation and secondary mechanisms. Thereafter, their quantity-effect relationship was speculated. These helped deepen the understanding of the time association and the crosstalk mechanisms.

Keywords: Hypertension; Initiating mechanism; Quantity-effect relationship; Secondary mechanism; Sympathetic nervous system

How to cite this article:
Ma ZY. Initiating and secondary mechanisms of hypertension along the time course. Cardiol Plus 2021;6:21-2

How to cite this URL:
Ma ZY. Initiating and secondary mechanisms of hypertension along the time course. Cardiol Plus [serial online] 2021 [cited 2021 Jun 23];6:21-2. Available from:

There are five classes of antihypertensive drugs: diuretics, beta-blockers, calcium channel blockers (CCBs), angiotensin-converting enzyme inhibitors (ACEIs), and angiotensin receptor blockers (ARBs). Kucan et al. analyzed the usage pattern of antihypertensive drugs. He found that the most frequently prescribed drugs in Croatia were ACEIs and ARBs, followed by CCB.[1] This may have been due to several factors, such as price and hypertension guidelines. According to the 2020 International Society of Hypertension Global Hypertension Practice Guidelines,[2] ACEIs (or ARBs) plus CCBs were highly recommended as the first-line treatment. This suggestion was established based on multiple reliable evidence. However, the main antihypertensive mechanisms of ACEIs, ARBs, and CCBs do not involve sympathetic nervous system (SNS) and salt-related mechanisms.

Hypertension is a disease with multiple mechanisms. According to Braunwald's Heart Disease,[3] these include the neural mechanisms (mainly referring to the SNS), renal mechanisms (mainly referring to the retention of sodium and water), vascular mechanisms (mainly referring to endothelial and vascular smooth muscle-related mechanisms), and hormonal mechanisms (mainly referring to the renin-angiotensin system [RAS]). SNS and sodium-related mechanisms are classified as initiating mechanisms in this hypothesis; these are stimulated externally, such as in states of nervousness, cold, and excess salt intake. Classified as secondary mechanisms in this hypothesis, vascular and RAS mechanisms are activated sequentially. The crosstalk mechanisms between the initiating and secondary mechanisms have been investigated in depth. However, the “quantity-effect” relationship between initiating and secondary mechanisms remains unknown. It is difficult to evaluate the “quantity-effect” relationship between comprehensive mechanisms. We made a hypothesis [Figure 1] to explain the current antihypertensive medication better and establish the management strategies for hypertensive patients.
Figure 1: Hypothesis of the relationship among hypertension mechanisms.
A, Initiating mechanisms are at a low level, and the damaging effect on blood pressure and target organ is low, although secondary mechanisms could magnify the effect. B, Initiating mechanisms are activated, and damage effects present while secondary mechanisms have not been overactivated.
C, Both initiating and secondary mechanisms are overactivated, and blood pressure and target organ damage reach a high level with the amplified effect of secondary mechanisms.
+: The positive feedback between the renin-angiotensin system and sympathetic nervous system. Small dots: Effect of initiating mechanisms, Large dots: Amplified effect of secondary mechanismsa

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The leading mechanism(s) behind a patient's hypertension varies depending on their age and hypertension stage. Expert consensus on hypertension management in the young and middle-aged Chinese population emphasized the importance of beta-blockers besides ACEIs, ARBs, and CCBs.[4] Based on the time scale, this suggested the early stage of a hypertensive patient before or during the onset of hypertension. In Panel A of [Figure 1], all mechanisms are at a low level. Panel A represents the early stage, characterized by high normal blood pressure, level 1 hypertension, and young and middle-aged hypertensive patients. Effective control of the initiating mechanisms at this stage leads to maintaining a low blood pressure level with few affected organs. Although, secondary mechanisms can exacerbate the damaging effect of initiating mechanisms. If initiating mechanisms are not controlled (Panel B), its cumulative effect will influence the secondary mechanisms while aggravating the blood pressure and target organ damage. Persistent failure to control the initiating mechanisms (Panel C) will cause the overactivation of the secondary mechanisms and, further amplifying the effect of initiating mechanisms. Both initiating and secondary mechanisms would exacerbate blood pressure and target organ damages. The amplification effect of secondary mechanisms increases organ damage and prolongs the timing of the mechanisms from impulse type or intermittent type of initiating mechanisms to persistent type of secondary mechanisms. Under Panel A, any antihypertensive drug can control blood pressure. Moreover, diuretics, beta-blockers, and protective mechanisms, such as lifestyle management, prevent patients from entering Panel B or C. Regardless of the initiating mechanisms, any antihypertensive drug will hardly reverse Panel C to A. Thus, combination therapy may be necessary.

This hypothesis does not speculate the progression of hypertension as the patient ages. Instead, it speculates the hypertension mechanisms from their occurrence to development. In the clinical setting, most hypertension patients seek consultation when they have already reached the Panel C stage since their blood pressure has already increased for several years. This hypothesis explains why ACEIs (or ARBs) and CCBs have outperformed diuretics and beta-blockers.

This hypothesis on the “quantity-effect” relationship and the time scale needs further evidence. Recent research hotspots mainly focused on RAS, vascular mechanisms, and their related inflammation mechanisms, which occur downstream the initiating mechanisms. It is still necessary to develop novel monitoring and intervention methods against initiating mechanisms to prevent, evaluate, and manage hypertension during the whole life course.

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There are no conflicts of interest.

  References Top

Kucan M, Mrsic-Pelcic J, Vitezic D. Antihypertensive drugs in Croatia: What changes the drug usage patterns? Clin Ther 2018;40:1159-69. doi: 10.1016/j.clinthera. 2018.05.018.  Back to cited text no. 1
Unger T, Borghi C, Charchar F, Khan NA, Poulter NR, Prabhakaran D, et al. 2020 international society of hypertension global hypertension practice guidelines. Hypertension 2020;75:1334-57. doi: 10.1161/HYPERTENSIONAHA.120.15026.  Back to cited text no. 2
Libby P, Zipes DP, Bonow RO, Mann DL, Tomaselli GF, Bhatt D. Braunwald's Heart Disease: A Textbook of Cardiovascular Medicine. Elsevier; 11 edition (March 6, 2018),ISBN-13: 978-0323463423.  Back to cited text no. 3
Liu J, Lu X, Chen L, Huo Y. Expert consensus on the management of hypertension in the young and middle-aged Chinese population. Int J Clin Pract 2019 Oct 1;e13426 doi: 10.1111/ijcp. 13426.  Back to cited text no. 4


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