Working group for the treatment of arterial hypertension of the European Society of Arterial Hypertension approved by the European Renal Association (ERA) and the International Society of Arterial Hypertension (ISH)
Abbreviations : ARB: angiotensin receptor blockers. BB: beta blockers. CCB: calcium channel blockers. CV: cardiovascular. RCT: randomized clinical trials. ET-1: endothelin-1. CKD: chronic kidney disease. AF: atrial fibrillation. HMOD: hypertension-mediated organ damage. LVH: hypertrophy of the left ventricle. HF: heart failure. HFpEF: heart failure with preserved ejection fraction. HFrEF: heart failure with reduced ejection fraction. ACEI: angiotensin converting enzyme inhibitors. MAP: Ambulatory Blood Pressure Monitoring. MRA: mineralocorticoid antagonists. LMWH: Home Blood Pressure Monitoring. BP: blood pressure. DBP: diastolic blood pressure. SBP: systolic blood pressure. RAS: renin angiotensin system. SGLT2is: SGLT2 inhibitors. RAAS: renin-angiotensin-aldosterone system
The year 2023 marks the 20th anniversary of the European Society of Hypertension (ESH) hypertension guidelines, which were first published in 2003, following a proposal by Professor Alberto Zanchetti.
These 2023 hypertension guidelines have also been prepared solely by the ESH. The rules in these guidelines, however, are largely, although not entirely, the same as those followed in the previous guidelines. Particular attention has been paid to scoring the robustness of diagnostic and treatment recommendations, which have been classified according to criteria partly different from those used in previous guidelines, i.e. taking into account the study design but also the quality of the data collected. Due to the questionable scientific value of voting, disagreements over treatment recommendations have not been resolved that way but by consensus in a shared text. Contradictory evidence or interpretations of data have been openly admitted.
Particular attention has been paid to real-world studies, which play an increasing role in hypertension research and sometimes provide insights into areas that cannot be addressed by randomized controlled trials (RCTs). Like the previous guidelines, the 2023 guidelines (i) view their value as educational, which explains why the text addresses the data justifying the recommendations, and (ii) emphasize that their recommendations are not invariably prescriptive for individual patients because They are based on average data and address general conditions or diseases. In individual patients, the most appropriate diagnostic and treatment decisions may differ from those expressed in the guidelines.
Principles of pathophysiology of arterial hypertension
High blood pressure is divided into primary forms (previously and still currently called "essential" ) and secondary forms . Secondary hypertension arises from specific causes and can be detected only in a small fraction of hypertensive patients). Primary hypertension covers the large remaining fraction of the hypertensive population, and its origin depends on the complex interaction between a genetic background, a large number of environmental factors and the aging process. Both genetic and environmental factors operate through alterations of the cardiovascular (CV) regulatory system, leading to increased systemic vascular resistance , which is the hallmark hemodynamic abnormality responsible for elevated blood pressure (BP) in almost all hypertensive patients.
In recent years, new and important evidence has been obtained on the genetic background of hypertension, identifying more than 1000 genetic factors, together with, in some cases, the biochemical and pathophysiological pathways by which they act. New environmental factors (e.g. air pollution and noise) have been added to those already documented by previous research. Furthermore, new clinical and experimental studies have confirmed that alterations in several major cardiovascular (CV) control systems may contribute to chronic elevation of blood pressure (BP). Primary hypertension may be accompanied by alterations in the renin-angiotensin-aldosterone system (RAAS), central and peripheral cardiac and autonomic vascular regulation, the endothelin system, and other systems that control vascular function, including nitric oxide and natriuretic peptides. . More recently, presogenic (increased sodium sensitivity) effects of gut microbial dysbiosis have also been reported .
Furthermore, the immune system is likely to play a pathophysiological role, with effects possibly being mediated primarily by inflammation and involving not only the regulation of BP (and therefore the development of arterial hypertension) but also the initiation and the progression of hypertension-mediated organ damage (HMOD). There is extensive experimental and clinical evidence that hypertension is associated with inflammation and immune cell activation, two processes that are largely driven by oxidative stress . Immune cell activation is characterized by excessive production of reactive oxygen species and an altered oxidation-reduction (redox) state, and there is evidence that the generation of reactive oxygen species is influenced by factors involved in the regulation of blood pressure (BP), such as Ang II, endothelin-1 (ET-1), aldosterone and salt (sodium).
Furthermore, there is also available evidence that alterations in immunoinflammation are promoted by the aforementioned promoters of hypertension, such as genetic susceptibility, neurohumoral activation, salt influences, and the gut microbiome. Although this complex interaction makes it impossible to know whether inflammation is causally related to hypertension or represents a side effect of chronic elevation of blood pressure (BP), it is clear that inflammation and a dysregulated immune system are closely related to each other. and that immunoinflammation is involved in high blood pressure. In fact, it has been suggested that oxidative stress and increased generation of reactive oxygen species represent the common molecular basis linking immunoinflammation with arterial hypertension.
Alterations in metabolomic pathways , for example glucose and lipid metabolism, may also contribute, as exemplified by the sympathostimulant effect of insulin and the favorable effect of sympathostimulation on insulin resistance.
Regardless of the mechanisms involved, with chronically elevated BP, the elevation is known to modify the structure of the heart (e.g., left ventricular hypertrophy (LVH)), large arteries (increased collagen and hardening of the arterial wall ) and small arteries (increased wall-to-lumen ratio), which in a later phase of hypertension promote an increase in blood pressure (BP) on a non-specific anatomical basis. This confirms and extends the ancient mosaic theory of the pathogenesis of primary hypertension as a multifactorial phenotype , which had already been formulated by Page in the pioneering phase of hypertension research more than 70 years ago. To the original theory, modern research has added not only new mechanisms but also strong evidence of the existence of reciprocal influences between different cardiovascular (CV) control systems, as a result of which alteration of one system can favor or reinforce alterations. of the other systems and vice versa.
On a practical level, this interactive multi-mechanism pathophysiology implies that diagnostic attempts to identify a single mechanism responsible for primary hypertension can often be not only methodologically difficult but also futile . It also explains why elevated blood pressure (BP) can be lowered by drugs with different mechanisms of action, as well as why a combination of mechanically different drugs reduces blood pressure (BP) much more effectively than monotherapy.
Definition and classification of high blood pressure
3.1 Definition of hypertension
According to previous European guidelines from 2018 and current international guidelines, arterial hypertension is defined based on repeated values of office systolic blood pressure (SBP) ≥140 mmHg and/or diastolic blood pressure (DBP) ≥90 mmHg . However, there is a continuous relationship between BP and morbid or fatal CV or renal events from an office systolic blood pressure (SBP) >115 mmHg and a diastolic blood pressure (DBP) >75 mmHg. Therefore, this definition is arbitrary and primarily serves the pragmatic purpose of simplifying the diagnosis and management decision of hypertension. In this context, the office threshold blood pressure (BP) values above correspond to the BP level at which the benefits of intervention (lifestyle interventions or drug treatment) outweigh those of inaction, such as This is shown by results-based randomized clinical trials (RCTs). Based on the available evidence, the definition of hypertension remains unchanged from previous guidelines.
3.2 Classification of hypertension
Classification of office BP and definition of degrees of hypertension also remain the same as previous guidelines (Table 1).
In addition to the degrees of hypertension, which are based on BP values, we also distinguish the stages of hypertension as follows:
Stage 1 : Uncomplicated hypertension (i.e., without hypertension-mediated organ damage (HMOD) or established CVD, including stage 1 and 2 chronic kidney disease (CKD)).
Stage 2 : Presence of HMOD or grade 3 chronic kidney disease (CKD) or diabetes.
Stage 3 : Established CVD or chronic kidney disease (CKD) stages 4 or 5.
Screening versus case finding in the detection of arterial hypertension
Due to the high prevalence of hypertension in the general population and its important role as a cause of death and morbidity, its detection is of vital importance for public health. Studies carried out in different countries have almost universally shown that a considerable fraction of hypertensive patients are unaware of their condition , which is negatively reflected in the number of patients who receive treatment and achieve BP control. There is evidence that screening policies can substantially increase the number of people with hypertension, although data on the benefits and harms are lacking from the results of randomized controlled trials or observational studies with low risk of bias. However, participation in selection procedures may be lower in some categories (e.g., men, younger people, people with lower socioeconomic levels) than in others.
In the US, the US Preventive Services Task Force suggests screening for hypertension in adults aged 18 years and older . Despite limited evidence on the optimal frequency of screening, they recommend annual screening in adults ≥ 40 years and in those at higher risk of developing hypertension, such as blacks, people with high-normal BP, and people who are overweight or obese. .
Opportunistic screening is also now encouraged in several countries and has recently been supported in the US by the increase in screening, treatment and control of hypertension associated with blood pressure (BP) measurements in barbershops or by pharmacists. . Based on available evidence, we recommend opportunistic screening for hypertension in all adults (i.e., ≥18 years). Regular BP measurement is particularly important in adults aged 40 years and older and in adults at increased risk of hypertension (special ethnic groups, individuals with high-normal BP, overweight or obese). Attention should be paid to postmenopausal women and women with a history of gestational hypertension and preeclampsia.
Blood pressure (BP) monitoring should always be part of any medical visit, even in people under 18 years of age.
Figure : Recommendations for office and home blood pressure (BP) measurements. to. Use an automated electronic device (oscillometric), validated according to an established protocol (www.stridebp.org). A device that automatically takes triplicate readings is preferred. b. Selection of an appropriate cuff size is crucial for accurate BP measurement and depends on the arm circumference of each individual: a smaller cuff than required overestimates BP and a larger one underestimates it. Using automated electronic devices, select the cuff size according to the device’s instructions. At the initial visit, measure BP in both arms. c. Measure in the morning and evening for 3 to 7 days. Use the average of all readings excluding the first day.
Confirmation of the diagnosis of hypertension
Due to blood pressure (BP) variability , an elevation in office BP (SBP ≥140 mmHg or DBP ≥90 mmHg) should be confirmed in at least two or three visits , unless the values recorded during the first visit are markedly elevated (grade 3 hypertension) or cardiovascular (CV) risk is high, including the presence of hypertension-mediated organ damage (HMOD). Although the available evidence has some diagnostic and clinical practice limitations, large-scale Ambulatory Blood Pressure Monitoring (ABPM) or Home Blood Pressure Monitoring (HBPM) data collection may be difficult. , out-of-office BP measurements are a source of important clinical information. Therefore, data should be collected whenever feasible when office BP is elevated, to confirm the diagnosis of arterial hypertension and identify specific BP phenotypes. ABPM and/or LMWH (home BP monitoring) may be especially important when office visit BP data provide variable results.
Characteristics of patients that should raise suspicion of secondary hypertension
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When to refer a hypertensive patient to a specialist or hospital • Patients in whom secondary arterial hypertension is suspected. • Young patients (<40 years) with grade 2 or 3 arterial hypertension in whom secondary hypertension must be excluded. • Patients with sudden onset or worsening of arterial hypertension when BP was previously normal. • Patients with high blood pressure resistant to treatment. • Need for more detailed evaluation of hypertension-mediated organ damage (HMOD), which could influence the treatment decision. • Requirement of a more in-depth specialized evaluation by the referring physician. • Hypertensive emergencies (hospital care will usually be needed). |
Antihypertensive treatment (drugs)
In the 2018 ESC/ESH guidelines, five major classes of drugs were recommended as first-line agents for the treatment of hypertension, i.e., angiotensin-converting enzyme inhibitors (ACE inhibitors), angiotensin receptor blockers ( ARB), calcium channel blockers (CCB), thiazides/thiazide-like diuretics and beta blockers (BB). However, the recommendations included two particular weightings within this group of drug classes. First, the use of a renin angiotensin system (RAS) inhibitor (ACE inhibitor or ARB), if not contraindicated, was considered a common component of the overall combination treatment strategy and, second, the use of beta blockers ( BB) was restricted to special clinical conditions or situations. The selection of these five drug classes was based on the following criteria:
1. A proven ability to lower blood pressure (BP) as monotherapy.
2. Evidence from randomized clinical trials (RCTs) that they reduce morbidity and mortality.
3. A favorable tolerability and safety profile.
On the basis of randomized clinical trials (RCTs) and their meta-analyses, the 2018 guidelines concluded that all the above drug classes met the required criteria, i.e., (i) they effectively lower SBP and DBP; (ii) reduce specific major outcomes associated with hypertension compared to placebo and (iii) exert a similar or only slightly different overall effect on the combined risk of major cardiovascular (CV) outcomes and mortality when administered as an initial step of treatment, although with some differences for some cause-specific outcomes (less stroke prevention with beta-blockers (BB) and angiotensin-converting enzyme (ACE) inhibitors), less heart failure prevention ( HF) with calcium channel blockers (CCBs) and greater prevention of HF with thiazide diuretics).
Other considerations were that (iv) the reduction in events is essentially due to blood pressure (BP) reduction per se rather than specific drug properties, meaning that the greater the number of drug options, the greater It will be the opportunity to adapt an effective treatment to reduce BP to the individual characteristics of the patient; (v) the antihypertensive effect of these five classes of drugs extends to Ambulatory BP Monitoring (ABPM) and Home BP Monitoring (HBPM); (vi) its BP-lowering ability and protective effect include use in combination with other drugs, as shown in RCTs in which BP-lowering treatment with multiple drugs was associated with reduced CV outcomes and (vii) the side effects of drug classes are largely related to the doses used and their differences between classes are minimized by the use of lower doses in the combination treatment.
These considerations and recommendations are shared by the present guidelines, which also share the subordinate position attributed to other antihypertensive drugs (alpha blockers, centrally acting agents), because these drugs have been less studied in outcome-based RCTs, or are se known to be associated with an increased risk of adverse effects. These drugs may be useful additions to the main arsenal of antihypertensives, in some specific cases, or when BP cannot be controlled by various combinations of the main drug classes.
In addition, mention is made of new classes of drugs , such as SGLT2 inhibitors (SGLT2is) and non-steroidal mineralocorticoid antagonists (MRAs), which are available and show BP-lowering effects. These effects may be less pronounced than those of classical antihypertensive drugs, but there is now strong evidence from RCTs that they reduce cardiovascular and renal events in patients with type 2 diabetes and, in the case of SGLT2 inhibitors (SGLT2is), also in patients without diabetes. New criteria for drug performance are also discussed, such as evidence of differences in treatment persistence and discontinuation rates between major drug classes and even between drugs or drug combinations within a given class. This is clinically relevant because discontinuation of antihypertensive treatment leads to increased CV outcomes. Accurate and correct prescriptions of medications for documented cardiovascular disease or other medical conditions are among the most important decisions physicians can make to maintain or improve adherence and persistence of prescribed medications. A synopsis of the major drug classes and additional drugs classified for BP-lowering therapy in hypertension is shown in Fig. 11.
What’s new? ( Original document index )
1. Modified and simplified criteria for evidence grading recommendations.
2. Pathophysiological history of primary hypertension.
3. Clinical BP measurements by different methods and in different clinical settings and conditions.
4. Detailed description of office, outpatient and home BP measurements and value in different demographic and clinical conditions.
5. Update of out-of-office BP measurements in the management of hypertension.
6. New measurements of HMOD and their clinical value in the study of hypertension
7. New CV risk factors and update of CV risk assessment.
8. Update and complete summary of secondary forms of hypertension.
9. Update on lifestyle interventions.
10. Update on the threshold and targets for antihypertensive drug treatment, including its possible heterogeneity in demographic and clinical subgroups of patients.
11. Confirmation of the preferred use of RAS blockers, CCBs and thiazide/thiazide-like diuretics, and their various combinations for BP lowering treatment. Inclusion of BBs among the main antihypertensive drugs
12. Update on available combination-based drug treatment strategies, including quadruple and polypill.
13. Emphasis and update on the diagnosis and management of true resistant hypertension.
14. Update on the use and position of renal denervation for antihypertensive treatment.
15. Impact of hypertension and its treatment on cognitive dysfunction and dementia.
16. Management of high blood pressure in older people according to frailty and functional level.
17. Update on the treatment of hypertension in heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF).
18. New diagnostic approaches for diagnosis and treatment in hypertensive patients with atrial fibrillation (AF).
19. Update on the treatment of chronic kidney disease (CKD), including kidney transplant.
20. Update and novel treatment approaches for patients with type 2 diabetes.
21. Epidemiology, diagnosis and treatment in different BP phenotypes.
22. Diagnosis, treatment and monitoring of hypertension in demographic and clinical conditions not or only marginally addressed in previous guidelines:
to. Childhood/adolescence and transition to adulthood
b. Young patients
c. Sex-related differences
d. Pregnancy and puerperium
and. Peripheral arterial disease
F. aortic aneurysm
g. Valvular heart disease
h. Treatment of hypertension in acute cerebrovascular diseases
Yo. Hypertensive emergencies/urgencies
j. Perioperative hypertension
k. Obesity
l. COVID-19
m. chronic inflammatory diseases
n. Hypertension in oncology
either. Baroreflex insufficiency and dysautonomia
p. Glaucoma
23. Detailed recommendations on patient follow-up strategies, including assessment and minimization of non-adherence and clinical inertia.
24. Mention of potential new approaches to the treatment of hypertension and containment of hypertension-related workload (telehealth, team-based treatment, role of pharmacists).
