Hypertension

Non-elevated blood pressure < 120/70

Elevated blood pressure 120-139/70-89

Hypertension > 140/90

Classes of Recommendations

Factors influencing BP Regulation

  • Blood pressure is the product of CO and PVR (peripheral vascular resistance)

  • CO is the product of SV and HR. Factors affecting CO: sodium intake, renal function, mineralocorticoids

  • PVR depends on the sympathetic nervous system (SNS), humoral factor and local autoregulation. The SNS produces its effects via vasoconstrictor alpha effect or the vasodilator beta effect

  • The humoral actions are a result of mediators, such as vasoconstrictors (e.g. endothelin, angiotensin II, catecholamines) or vasodilators (e.g. nitric oxide, prostaglandins, kinins)

Arterial Hypertension Classification

The classifications are depending on:

  1. Etiology

    • Primary

    • Secondary

Pathogenesis of Primary Hypertension

The pathogenesis of primary hypertension is a complex interplay between

  • genetic predisposition,

  • lifestyle and environmental influences,

  • disturbances in vascular structure and neurohumoral control mechanisms.

  • Activation of the sympathetic system

  • Activation of renin-angiotensin-aldosterone system

A characteristic finding is an inappropriate increase in peripheral vascular resistance relative to the cardiac output

  • This is due to remodelling of small arteries (arterioles), - an increase in their media/lumen ratio

  • The functional integrity of large conduit arteries, i.e. the aorta, which becomes stiffer, also influences the development of hypertension— especially systolic hypertension

Cardiovascular Disease risk factors

  • Male sex

  • Age ( ≥ 55 years in men; ≥ 65 years in women)

  • Smoking

  • Dyslipidaemia (general population)

  • Fasting plasma glucose 5.6 – 6.9 mmol/l (102 – 125 mg/dl)

  • Abnormal glucose tolerance test

  • Diabetes

  • Obesity (BMI ≥ 30 kg/m²)

  • Abdominal obesity: waist circumference ≥ 102 cm in men; ≥ 88 cm in women (Caucasians)

  • Family history of premature CV disease ( < 55 yrs in men; < 65 yrs in women)

Factors influencing cardiovascular risk in patients with hypertension

  • Uric acid

  • Family or parental history of early-onset hypertension

  • Early-onset menopause

  • Sedentary lifestyle

  • Psychosocial and socioeconomic factors

  • Heart rate (resting values >80 beats/min)

Clinical Consequences of AH

Longstanding hypertension causes organ damage and ultimately leads to cardiovascular, cerebrovascular, and clinical renal disease

Organs affected by elevated BP and hypertension:

  • Brain

  • Heart

  • Kidneys

  • Eyes

  • Vessels (macrocirculation and microcirculation in organs with low resistance, such as the brain or kidney

Consequences of these developments:

  • Cardiovascular diseases

  • Cerebrovascular diseases

  • Kidney failure

Blood pressure assessment methods

Office blood pressure measurement

  • quiet environment for 5 mins seated comfortably before measuring

  • 3 BP measurements should be taken 1-2 minutes apart

  • arm should be supported

  • use phase 1 and V Korotkoff sounds to identify SBP and DBP

  • first visit: measure both arms (difference 5-10 mmHg, coarctation of aorta, pathologies in aorta/big arteries), lying and standing to avoid orthostatic AH - Difference should be 20mmHg

Home-based blood pressure measurement

  • average of all BP readings performed with a semiautomatic, validated BP monitor, for at least 3 days

  • in morning and evening, quiet room after 5 mins rest, seated, arm rested. Two measurements 1-2 mins apart

  • usually lower compared to office BP. diagnostic threshold for hypertension is ≥135/85mmHg

Ambulatory blood pressure measurement

  • ABPM provides the average of BP readings over a defined period, usually 24 h

  • The device is typically programmed to record BP at 15 - 30 min intervals, and average BP values are usually provided for daytime, night-time, and 24 h

Specific situations

White coat hypertension

The untreated condition in which BP is elevated in the office, but is normal when measured by ABPM, HBPM, or both

  • More common with increasing age, in women, and in non-smokers

  • Both ABPM and HBPM are recommended to confirm white-coat hypertension

Masked hypertension

Refers to untreated patients in whom the BP is normal in the office, but is elevated when measured by HBPM or ABPM

  • Greater in younger people, men, smokers, and those with higher levels of physical activity, alcohol consumption, anxiety, and job stress

  • Obesity, diabetes, CKD, family history of hypertension, and high–normal office BP are also associated with an increased prevalence of masked hypertension

Diagnosis

Hypertension diagnosis can`t be established based on one-time office blood pressure measurement.

Hypertension should be confirmed with repeated data: - preferably by ambulatory or home-based BP measurements

  • If BP > 180/110 mmHg – Hypertensive emergencies have to be excluded.

  • If it isn`t a Hypertensive emergency, repeated control should be obtained within a week. Treatment can be postponed until the next scheduled visit

Assessment of cardiovascular disease risk

The control/treatment of elevated BP and Hypertension treatment tactics depend on cardiovascular diseases (such as myocardial infarction, cerebral infarction and others) risk.

CV diseases risk depends on:

  • BP level

  • CV risk factors

  • Hypertension-mediated organ damage (HMOD)

  • Symptomatic cardiovascular and renal diseases

Elevated BP

Step 1. Assessment of sufficiently high CV risk conditions

Hypertension mediated organ damage

Heart

  • The most commonly used simple criteria and recognised cut-off points for definitions of electrocardiogram left ventricular hypertrophy, LA dilation (duration of P wave in lead II more than 120ms), arrythmias, blocks

Biomarkers: Hs-cTnT (high sensitive troponin) or TnI >99th percentile upper reference limit ▪ NT-proBNP > 125 pg/mL if aged <75 years, >450 pg/mL if aged ≥75 years.

Vessels

Pulse wave velocity

Carotid-femoral PWV > 10 m/s - shows how stiff arteries are

Brachial–ankle PWV > 14 m/s

ankle-brachial index - if less than 1 = normal

Carotid Ultrasound

Plaque (focal wall thickening > 1.5 mm). - see atherosclerosis!!

Computed Tomography (CT)

Calcium score > 100 Agatson units

Kidneys

  • eGFR < 60 ml/min/1,73 m² or

  • Urine Albumin-creatinine ratio > 30 mg/g

Step 2. Estimation of predicted 10-year CV risk

SCORE

  • Estimation of predicted 10-year CV risk

  • Criteria:

    1. regional CV mortality (WHO data)

    2. sex

    3. age

    4. blood pressure level

    5. non-high cholesterol /non-HDL cholesterol

    6. smoking

Step 3. Assessment of sex-specific and shared risk modifiers

Step 4. Consider additional examinations for CV risk assessment

Secondary Hypertension

  1. Renal

  • Pathologies of the parenchyma

    • chronic kidney diseases

    • acute glomerulonephritis

      chronic pyelonephritis

    • polycystic kidney disease

    • diabetic nephropathy

    • hydronephrosis

  • Renovascular hypertension

    • stenosis of A.renalis( unilateral, bilateral)

  1. Endocrine system pathologies

  • Acromegaly

  • Hypothyroidism

  • Hyperthyroidism

  • Pathologies of the adrenal gland:

    • cortex: Cushing syndrome, primary aldosteronism

    • medulla: pheochromocytoma

  1. Drug induced:

    • corticosteroids

    • hormonal contraceptives

    • sympathomimetics

    • nonsteroidal anti-inflammatory drugs

    • erythropoietin

  2. Coarctation of aorta, aortitis

  3. Pregnancy hypertension

  4. Neurological pathologies:

    • increased intracranial pressure (tumour, encephalitis); sleep apnoea etc.

  5. Perioperative hypertension

Patient characteristics that should raise the suspicion of secondary hypertension

  • Younger patients (<40 years) with grade 2 hypertension or onset of any grade of hypertension in childhood

  • Acute worsening hypertension in patients with previously documented chronically stable normotension

  • Resistant hypertension

  • Severe (grade 3) hypertension or a hypertension emergency

  • Presence of extensive Hypertension mediated organ damage (HMOD)

  • Clinical or biochemical features suggestive of endocrine causes of hypertension or Chronic kidney disease

  • Clinical features suggestive of obstructive sleep apnoea

  • Symptoms suggestive of phaeochromocytoma or family history of phaeochromocytoma

Hypertensive emergencies

Hypertensive emergencies are situations where very high BP values are associated with acute hypertension-mediated organ damage, and therefore, require immediate BP reduction to limit extension or promote regression of target organ damage

  • Key target organs of acute hypertension-mediated damage are the heart, retina, brain, kidneys, and large arteries

  • The type of target organ damage is the principal determinant of the choice of treatment, target BP, and timeframe by which BP should be lowered

Clinical Presentations of Hypertensive emergencies

  • Malignant hypertension - a hypertensive emergency characterized by the presence of a severe BP elevation (usually >200/120 mmHg) and advanced retinopathy, defined as the bilateral presence of flame-shaped haemorrhages, cotton wool spots, or papilloedema

  • cerebral infarction

  • Hypertensive encephalopathy - When BP is markedly elevated and cerebral autoregulation cannot prevent a rise in intracranial pressure, cerebral oedema may develop, especially in the posterior areas of the brain where sympathetic innervation is less pronounced leading to less effective damping of BP oscillations.

  • Hypertensive retinopathy

  • intracranial haemorrhage

  • acute left ventricular failure

  • acute pulmonary oedema

  • aortic dissection

  • acute renal failure

  • eclampsia

Diagnostic studies in patients with suspected hypertensive emergency

!!Blood tests

!!ECG - LVH LA dilation, arrythmias, blocks

!!Echocardiogram - signs of wall thickening, IV septum, diastolic function

Uncontrolled hypertension or Hypertensive urgencies

Is defined as large elevation in SBP and/or DBP associated without signs of the organ damages , just subjective or mild objective symptoms such as:

  • nasal bleeding

  • nausea, vomiting

  • headache, dizziness

  • chest pain

Resistant hypertension

Is defined as resistant to treatment when the recommended treatment strategy fails to lower office SBP and DBP values to < 140 mmHg and/ or < 90mmHg respectively, and the inadequate control of BP is confirmed by ABPM or HBPM in patients whose adherence to therapy has been confirmed.

The recommended treatment strategy should include appropriate lifestyle measures and treatment with optimal or best-tolerated doses of three or more drugs, which should include a diuretic, typically an ACE inhibitor or an ARB, and a CCB

Pseudo-resistant hypertension and secondary causes of hypertension should also have been excluded

The reasons of a true resistant hypertension:

  • Lifestyle factors such as obesity or large waist gains, excessive alcohol consumption and high sodium intake

  • Chronic intake of vasopressors, sodium retaining substances

  • Obstructive sleep apnoea

  • Undetected secondary forms of hypertension

  • Advanced and irreversible organ damages

Diagnostic approach to resistant hypertension

Pseudo-resistant hypertension

The reasons of pseudo RH:

  1. Poor adherence to prescribed medicines is a frequent cause of pseudo-resistant hypertension

  2. White-coat phenomenon (in which office BP is elevated but BP is controlled at ABPM or HBPM) is not uncommon in these patients

  3. Poor office BP measurement technique, including the use of cuffs that are too small relative to the arm circumference, can result in a spurious elevation of BP.

  4. Marked brachial artery calcification, especially in older patients with heavily calcified arteries

  5. Clinician inertia, resulting in inadequate doses or irrational combinations of BP-lowering drug therapies - doctors not giving enough dose of the medication

Classes recommendation and levels of evidence

Treatment of elevated blood pressure / hypertension

Two main treatment strategies:

  • Lifestyle interventions - can lower BP and in some cases CV risk, but most patients with hypertension will also require drug treatment

  • Pharmacological therapy

Data-based therapy

Non-pharmacological treatment of blood pressure and cardiovascular risk reduction

Physical Activity

Physical activity according to different types of exercise and reduction of blood pressure and overall cardiovascular disease risk.

Pharmacological Therapy (Drugs)

Main groups (first line):

  • Diuretics (thiazides and thiazide- like)

  • Angiotensin-converting enzyme inhibitors (ACEI)

  • Calcium channel blockers - dihydropyridine (CCB-DHP)

  • Angiotensin receptor blockers (ARB)

  • Beta-blockers (BB)

Others:

  • Mineralocorticoid receptor antagonists (MRAs)

  • Alpha -1- blockers

  • Central action drugs - methyldopa, clonidine, imidazoline receptor blockers

  • Loop diuretics

  • Alfa and beta receptor blockers

  • Direct vasodilatators (nitroglicerin, nitroprusid)

Recommendations for pharmacological treatment of hypertension

BP treatment targets

The first objective of treatment should be to lower BP to < 140/90 mmHg in all patients

Provided that the treatment is well tolerated, treated BP values should be targeted to 120-129/70 -79 mmHg

  • Personalised BP treatment targets can be instituted for people aged ≥85, those with moderate - -significant frailty at any age, and those with a limited predicted lifespan

  • In cases where BP-lowering treatment is poorly tolerated and achieving a systolic of 120–129 mmHg is not possible, it is recommended to target a systolic BP level that is ‘as low as reasonably achievable’

Angiotensin-converting enzyme inhibitors (ACEI) and Angiotensin receptor blockers (ARB)

Most widely used classes of antihypertensive drugs

Similar effectiveness as each other

  • ACE inhibitors and ARBs should not be combined for the treatment of hypertension - no added benefits, excess of renal adverse events

  • ACE inhibitors and ARBs reduce albuminuria, are effective at delaying the progression of diabetic and non-diabetic CKD, effective in preventing or regressing HMOD - such as LVH and small artery remodelling, reduce incident AF, indicated postmyocardial infarction and in patients with chronic HFrEF.

Calcium channel antagonists - dihydropyridine (CCB-DHP)

Widely used for the treatment of hypertension and have similar effectiveness as other major drug classes on BP

CCBs are a heterogeneous class of agents

  • CCBs have a greater effect on stroke reduction than expected for the BP reduction achieved, less effective at preventing HFrEF

  • More effective than beta-blockers in slowing the progression of carotid atherosclerosis, and in reducing LVH and proteinuria

Thiazide/thiazide-like diuretics (e.g. chlorthalidone and indapamide)

  • Diuretics appear to be more effective than other drug classes in preventing heart failure

  • Exhibit dysmetabolic effects that increase insulin resistance and the risk of new-onset diabetes

  • Both thiazides and thiazide-like agents are less effective antihypertensive agents in patients with a reduced GFR

  • In such circumstances, loop diuretics such as furosemide (or torasemide) should replace thiazides and thiazide-like diuretics to achieve an antihypertensive effect

Beta-blockers

Beta-blockers significantly reduce the risk of stroke, heart failure, and major CV events in hypertensive patients.

  • Beta-blockers are usually equivalent in preventing major CV events, except for less effective prevention of stroke

  • Beta-blockers are useful for the treatment of hypertension in specific situations such as symptomatic angina, for heart rate control, post-myocardial infarction, HFrEF, and as an alternative to ACE inhibitors or ARBs in younger hypertensive women planning pregnancy or of child-bearing potential

  • Beta-blockers are less effective than RAS blockers and CCBs in preventing or regressing LVH, carotid IMT, aortic stiffness, and small artery remodelling.

  • Beta-blockers are also associated with increased risk of new-onset diabetes in predisposed subjects

Drugs contraindications and special precautions

The Drug Treatment Algorithm for Hypertension

  1. The initiation of treatment in most patients with an Single-pill Combination (SPC) comprising two drugs to improve the speed, efficiency, and predictability of BP control

  2. Preferred two-drug combinations are a RAS blocker with a CCB or a diuretic. A beta-blocker in combination with a diuretic or any drug from the other major classes is an alternative when there is a specific indication for a beta-blocker, e.g. angina, post-myocardial infarction, heart failure, or heart rate control.

  3. The Monotherapy can be used for patients aged ≥ 85, those with symptomatic orthostatic hypotension, moderate-to-severe frailty or elevated BP (120- 139/70-89 mmHg)

  4. The use of a three-drug SPC comprising a RAS blocker, a CCB, and a diuretic if a two-drug SPC does not control BP

  5. The addition of spironolactone for the treatment of resistant hypertension, unless contraindicated

  6. The use of other classes of antihypertensive drugs in the rare circumstances in which BP is not controlled by the above treatments

Device-based hypertension treatment

Use of device-based therapies is not recommended for the routine treatment or the first-line therapy of hypertension unless in the context of clinical studies and RCTs until further evidence regarding their safety and efficacy becomes available

Method:

  • Renal denervation

    • Bilateral destruction of the renal nerves travelling along the renal artery by radiofrequency ablation catheter

    • This causes reduction of sympathetic afferent and efferent activity to the kidney and blood pressure can be decrease

Hypertensive emergencies requiring immediate BP lowering

Intravenous (i/v) administration

Hypertensive urgencies- treatment

Per oral administration (p/o)

Recommended pharmacological treatment of Resistant Hypertension

  • Reinforcement of lifestyle measures, especially sodium restriction

  • Addition of low-dose spironolactone to existing treatment

  • Or the addition of further diuretic therapy if intolerant to spironolactone, with either eplerenone, amiloride, a higher dose thiazide/thiazide-like diuretic, or a loop diuretic

  • Or the addition of bisoprolol or doxazosin

Management of resistant hypertension