hypertension

• Hypertension


  Higher than normal blood pressure

  
• Normal blood pressure


  • Heart rate : Blood pressure = blood flow x vessel resistance
  • Resistance is inversely proportional to radius^4 (Poisseuille law)

  
• Classification of Hypertension


  • Primary Hypertension (Essential): Unknown Aetiology
  • Secondary Hypertension (Non-Essential): Known Aetiology
  • Renal Hypertension
  • Endocrine Hypertension
  • Hypertension of Pregnancy
  • Iatrogenic Hypertension

  
• Signs and symptoms of hypertension

  • Generally no signs or symptoms of hypertension
  • Can be difficult therefore for patients to adhere or want to take medication
  • In extreme cases (180/90mmHg and above): Severe headache, fatigue or confusion, vision problems, arrhythmias, pounding sensation (chest, neck, ears), chest pain/discomfort, difficulty breathing, blood in urine
  • If left untreated may present with: organ damage, stroke, heart attack, failure or disease, dementia, peripheral arterial disease

  
• Risk factors for Essential Hypertension

  • Age
  • Race
  • Gender
  • Family History
  • Sedentary lifestyle
  • Poor diet
  • High sodium diet
  • Obesity
  • High alcohol consumption
  • Smoking
  • Stress
• Objectives of Hypertension Therapy

  • Not just to reduce BP - to reduce cardiovascular outcomes of hypertension
  • BP not only factor in deciding therapy
  • Outcome data is essential
  • Risk/benefit analysis is critical
  • Need to achieve long term, 24hour reductions in BP. Monitoring critical

  
• Holistic measures for hypertension

  • Maintain normal weight for adults (body mass index 20-25 kg/m2)
  • Reduce salt intake to <100 mmol/day (<6g NaCl or <2.4 g Na+/day)
  • Limit alcohol consumption to no more than 14 units/week (CMO guidance)
  • Engage in regular aerobic physical exercise (brisk walking rather than weight lifting) for 30 minutes per day, ideally on most of days of the week but at least on three days of the week
  • Consume at least five portions/day of fresh fruit and vegetables
  • Reduce the intake of total and saturated fat
  • Reduce stress
  • Stop smoking
• Risk assessment for hypertension

  1. Urine dip for protein and blood

  2. ACR (albumin to creatinine ratio)

  3. Bloods for: U and Es, Cholesterol and lipid profile, HbA1c (blood glucose)

  4. Optometrist: fundoscopy to view retina for damage

  5. 12 lead ECG

  6. QRISK 3 score for 10yr CVD risk assessments (https://qrisk.org/three/)

  7. More detailed review required in: HIV,CKD, SLE and other autoimmune disorders, familial hypercholesterolemia, those under 40 with stage 1 HTN

  
• Blood Pressure Thresholds for Diagnosis and Treatment of Hypertension

  • Stage 1 Hypertension: Clinic BP ≥140 /90 but <160/100, 24hr Daytime ABPM Average ≥135/85, Home ABPM Average ≥135/85
  • Stage 2 Hypertension: Clinic BP ≥160 / 100, 24hr Daytime ABPM Average ≥150/95, Home ABPM Average ≥150/95
  • Severe Hypertension: Clinic BP ≥180/110
  • Accelerated Hypertension: Usually Clinic BP ≥180/110 + retinal haemorrhages and/or papilloedema

  
• Thresholds for Diagnosis and Treatment of Stage 1 Hypertension

  1. If patient under the age of 80 years, has target organ damage, renal disease, diabetes, CVD, or 10yr CVD risk ≥20% - Treat

  2. If patient under the age of 80 years, no target organ damage, renal disease, diabetes, CVD, and 10yr CVD risk <20% - Lifestyle and review 1 yr

  3. If over 80, consider treatment if BP > 150/90mmHg in addition to lifestyle factors

  4. For people aged <40ys, 10yr CVD risk assessments underestimate lifetime risk - consider referral for exclusion of secondary causes and more detailed assessment

  
• Stage 2 Hypertension - Treat (any age, taking into account frailty)

  
• Blood Pressure Treatment Targets

  • Use Clinic BP to monitor BP control
  • Optimal Clinic BP control is <140/90mmHg
  • In people with "white coat effect", i.e. clinic BP is ≥20/10mmHg more than ABPM or Home average, use Home BP average to monitor treatment - target home BP average of <135/85mmHg
  • Review BP control at least annually once BP treatment is stable
• The Ideal Antihypertensive


  • Slow, controllable onset of action
  • Sustained control - supine & standing
  • 12-24 hr duration of action - compliance
  • Orally active (for long term therapy)
  • No -ve inotropic action/ reflex bradycardia
  • No adverse reactions - suitable long term
  • No development of tolerance
  • Beneficial effects on morbidity & mortality
• Resistance Hypertension


  • A clinic blood pressure that remains higher than 140/90 mmHg with the optimal or best tolerated doses of a drug from groups A, C and D
  • Expert advise may be needed and further review to exclude endocrine and other causes of hypertension
  • After this agents used may be from other groups such as: Beta Blockers, Alpha blockers, Spironolactone, Vasodilators

  
• ACE Inhibitors in Hypertension (group A)


  • Haemodynamically arterial vasodilators: all agents are equally effective, BP reduction does not correlate with changes in plasma renin or AII, some effect in anephric individuals
  • Best haemodynamic profile of the vasodilators: increase in renal blood flow, cerebral and coronary flow well maintained, improve arterial compliance (SBP), cardiac function well maintained
  • Aldosterone release well controlled (plasma K+ - care with drugs affecting)

  
• Advantages of ACE Inhibitors

  • Effective - equal reduction DBP to all other antihypertensives greater effect on SBP
  • Generally well tolerated, high acceptability - No adverse metabolic effects
  • Regression of LV hypertrophy and of vascular remodelling
  • Highly beneficial in LV systolic dysfunction - use in all hypertensives with LV systolic dysfunction even if asymptomatic
  • Retard progression of diabetic nephropathy - use in all patients with nephropathy, All diabetics?
• Disadvantages of ACE Inhibitors

  • Deterioration of renal function in renal stenosis - bilateral and unilateral one kidney. (care in PVD). May be exacerbated by NSAIDs
  • ACE is not selective for angiotensin formation. Reduced metabolism of kinins &neuropeptides: Skin rashes - usually maculopapular overall 5%, Dry Cough - incidence 15-20%, Angioneurotic Oedema (0.1-0.2%) Serious
  • Foetopathic potential: 2nd and 3rd trimesters, oligohydramnios, foetal death, growth retardation
  • Hyperkalaemia
• Angiotensin Receptor Blockers (ARB) – group A


  • Competitive antagonists at AT1 receptors
  • More precise pharmacological control of RAS
  • Highly selective - no effect on kinins, on SNS
  • Well tolerated: slow onset of action with minimal first dose effect
  • Do not produce cough associated with ACE-I
  • Otherwise similar to ACE-I: do not use in pregnancy, in renal failure (GFR <20ml/min), if there is renal artery stenosis etc.
• Renin Antagonist – Aliskiren

  • Directly inhibits renin
  • Essential hypertension
  • Similar side-effect profile as ACE inhibitors/Ang II
  • Not recommended for use with ACE inhibitor/Ang II
  • ALTITUTE study found adverse CV and renal events when used in combination with ACE inhibitor/Ang II
  • In practice rarely used- very select patient under specialist advice
  • Not for use with P-gp inhibitors
  • Interaction with Grapefruit juice - No fruit juices to be taken at same time
  • NICE guidelines do not recommend the use of aliskiren
  • Used as a reserve agent when others fail to achieve control
• Calcium Entry Blockers (Group C)

  • CEBs are one of a group of Vasodilators
  • Block voltage gated (L type) Ca2+ channel
  • Main groups differ in vascular selectivity - verapamil (least) - dihydopyridines (max). Dihydropyridines most widely used – reduce TPR
  • Direct action on VSM to reduce TPR, effect actions of all vasoconstrictors - not receptor antagonists (distal action), action independent of sympathetic tone
  • Good haemodynamic profile - increase RBF & maintain or improve renal function, maintain cerebral and coronary flow
  • Effective anti-hypertensives - used for chronic control but also may be used for rapid reduction in BP (Acute Control) e.g. hypertensive emergency or surgical control of BP
• The Dihydropyridines


  • Nifedepine - rapid action, starts in 20 min with half-life of 3hrs. MR/SR preps
  • Amlodipine - slow onset, half life 35-48hrs. Once daily dose
  • Nicardipine and Felodipine most vascular selective
  • Nimodipine – mainly used for Sub-arachnoid haemorrhage
• Advantages & Disadvantages of Dihydropyridines

  • Advantages: Effective - comparable with other major agents, may be used in asthma or COPD, peripheral vascular disease, gout, diabetes mellitus, positively indicated in cerebrovascular disease, peripheral vascular disease
  • Disadvantages: Number of side-effects due to vasodilatation - facial flushing, headache, nausea, ankle oedema, myocardial depression with verapamil, Coronary Ischaemia with short-acting DHPs
• Diuretics in hypertension (Group D)

  • Thiazides most widely used - Alone will control BP in about 50% of all essential hypertensives. Adding other diuretics does not improve efficacy. A flat dose-response curve with maximum antihypertensive effect around 2.5 mg Bendroflumethiazide. Linked to diuresis (no effect in anephric patients, dependent on Na+ intake) but different dose-response relationship
  • Loop diuretics. Torasemide only loop licensed for hypertension used when renal function is poor (GFR<60% normal, serum creatinine >150mM/L). Remember primary use of loop is fluid removal

  
• Mechanism of Action of Diuretics

  • Onset of antihypertensive slow - max at around 12 weeks. Early fall in cardiac output (CO) and extracellular fluid volume (ECFV) (typical 10%)
  • At peak antihypertensive action, fall in TPR. Attributed to autoregulation of tissue blood flow (normalises CO and tissue blood flow)
  • Antihypertensive action reduced by NSAIDs
  • Undesirable Effects minimised by low dose – ↓ K/Na/Mg/Ca, glucose intolerance, hyperuricaemia and hyperlipoproteinaemia
• Diuretics


  • Thiazides
  • Loop diuretics
• Thiazides


  Most widely used diuretics, alone will control BP in about 50% of all essential hypertension, adding other diuretics does not improve efficacy
• Thiazides


  • Flat dose-response curve with maximum antihypertensive effect around 2.5 mg Bendroflumethiazide
  • Linked to diuresis (no effect in anephric patients, dependent on Na+ intake) but different dose-response relationship
• Loop diuretics


  Used when renal function is poor (GFR<60% normal, serum creatinine >150mM/L), primary use is fluid removal
• Torasemide


  Only loop diuretic licensed for hypertension
• Mechanism of action of diuretics

  1. Onset of antihypertensive effect is slow - max at around 12 weeks

  2. Early fall in cardiac output (CO) and extracellular fluid volume (ECFV) (typical 10%)

  3. At peak antihypertensive action, fall in total peripheral resistance (TPR) attributed to autoregulation of tissue blood flow (normalises CO and tissue blood flow)

  4. Antihypertensive action reduced by NSAIDs
• Undesirable effects of diuretics

  • Minimised by low dose - ↓ K/Na/Mg/Ca, glucose intolerance, hyperuricaemia and hyperlipoproteinaemia
• Positive indications for diuretics

  • Old age
  • Congestive heart failure
  • For loop diuretics (as add on therapy to thiazides)
• General advantages of diuretics

  • Cheap
  • Widely effective
  • Generally well tolerated
  • Substantial evidence base
• Negative indications for diuretics

  • Diabetes mellitus
  • Gout
  • Obesity
  • Hyperlipidaemia
  • Where hypokalaemia may be a problem e.g. cardiac dysrhythmias
• Chlortalidone and indapamide


  Preferred over bendroflumethiazide or hydrochlorothiazide, as recent trials showing benefits used these thiazide-like diuretics
• No need to change diuretic in people stable on treatment and in whom BP is controlled (Unless causing side-effects or falls)
• Anti-sympathetic drugs


  • Autonomic ganglion blocking agents
  • Adrenergic neurone blocking agents
  • α1-adrenoceptor antagonists
  • β-adrenoceptor antagonists
  • Centrally acting α2-agonists
• β-adrenoceptor antagonists


  Not designed as antihypertensives, antihypertensive action associated with action at β1-adrenoceptors, many undesirable actions linked to effects at β2-adrenoceptors
• Indications for β-adrenoceptor antagonists

  • Younger people
  • Women of childbearing potential
  • Where there is evidence of sympathetic drive
  • Where intolerance to ACEI or ARB antagonists
  • Where there is a compelling reason to use e.g. Angina
• No reason to withdraw β-adrenoceptor antagonists where BP is controlled, if withdrawing do so slowly