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Bay Four

          Patterns, pearls and practical medicine

Hypertension: Diagnosis and management

The facts and stats

  • Overall, around 30% of adults in UK have HTN
  • 10% of people in their 30s have HTN. This rises to around 50% of those in their 60s.
  • Around 30% undiagnosed. Around 30% properly controlled. Around 30% aware but not on treatment, or BP still not controlled on treatment
  • The leading risk factor for disease burden. Increases risk not just of CV disease and stroke, but also all forms of dementia, not just vascular dementia, CKD and CCF
  • Every 10mm reduction in systolic BP reduces the risk of a major CV event by 20% (higher for HF and stroke), and a 13% reduction in all cause mortality. Reducing BP even if 130 systolic is beneficial for health.
  • The higher a patient’s baseline absolute CV risk, the greater the net benefit to lowering BP (and the lower NNT on a population level).
  • The relative CV risk reduction by a fixed BP reduction is largely independent of pre-treatment/baseline BP however
  • Elevated systolic blood pressure has a closer association with CV risk than diastolic
  • Afro-Caribbean patients have a greater prevalence of low-renin, salt-sensitive hypertension
  • Risk factors include older age, Afro-Caribbean ethnicity, genetic predisposition (40% of BP variability explained by genetics), social deprivation, co-existing CKD or DM, lifestyle factors, stress
  • Up to age 65, men have higher average BP, from 65-74, women have higher BP

Definitions

  • HTN most often defined as:
      • >140/90 in clinic
      • or >135/85 home BP
      • or >130/80 24-hour ambulatory BP
  • However definitions vary by guideline, as BP is normally distributed and cut offs are decided differently
  • In the US >130/80 is classed as hypertensive – which makes >half the adult population hypertensive
  • ESC guidelines also include an ‘elevated BP’ category, between normal and HTN
  • White coat HTN = a discrepancy of >20/10 between clinic and daytime average ambulatory BP
  • Masked HTN = normal clinic BP, but higher BP when taken at home or via ambulatory testing

Technique

  • Ensure five minutes of rest prior, and no exercise/caffeinated/smoking drinks for 30 minutes prior
  • Ensure no distended bladder
  • Ensure patient at rest ie not talking or actively listening
  • Arm supported
  • Check pulse (AF can affect reliability of measurements)
  • Measure BP both arms initially (if difference is >15mmHg, repeat, if still a big discrepancy, use arm with higher BP for future readings)
  • Use correct cuff size (undersized elevates BP)
  • Take 2 readings 1-2 mins apart. If big difference, take a 3rd. Record the lower of the last two readings
  • Consider checking for postural drop (>20/10mmHg on standing, taken at 1 and 3 minutes)
  • For home BP monitoring – check BP twice daily, at roughly same times, for 7 days. Keep a record.

Screening

  • Offer ambulatory or home BP measurement for those with BP 140/90-180/120 to confirm diagnosis
  • Home measurements – take BP twice daily for 7 days. Discard 1st day measurements
  • Screen annually if
      • Aged >40
      • Borderline HTN
      • BP controlled on medication
  • Screen every 3-5 years if <40 and low CV risk
  • Cuffless BP monitoring eg by photoplethysmography
      • Probably not quite accurate enough yet, but close
      • Still needs calibration with cuff (and for those who react to the cuff with BP spikes, maybe not that useful)
      • Evidence still to be gathered

Assessment of confirmed HTN

  • If clinic BP between 140 and 179 systolic – offer ambulatory or home BP monitoring
  • If BP >180 systolic – see severe hypertension
  • But generally speaking – don’t be in too much of a hurry to lower the BP, unless BP is the primary problem
  • Explanation (this is key, as understanding impacts future behaviour)
      • Only 1 in 10 patients with HTN have a cause we can identify
      • For most people, the cause of HTN is a complicated combination of factors (involving the environment, habits and lifestyle, genetics, hormones and various organs and body systems incl the heart and blood vessels, kidneys, nervous system, immune system. Some of these we can control, some we can’t
      • Most people feel well with HTN, but it’s still important to treat to reduce risk of health problems down the line – this includes heart issues, stroke, kidneys problems and dementia
      • We can reduce BP though medications and behaviour change, which reduces the risk to you
      • If medication is recommended, it’s important to take every day even if you feel well. Once started, it’s often used long term
      • Ask whether they have any concerns about taking tablets
  • Consider red flags
      • Sudden onset HTN
      • Symptoms – Chest pain, palpitations, headache, confusion, heart failure
      • Signs of end organ damage – uACR, eGFR, fundi, ECG
      • >180 SBP – Refer these for same day assessment if co-existent concerning symptoms/end organ damage
  • Investigations
      • All-comers
          • ECG
          • Renal profile, FBC, TFTs, lipids, HbA1c or fasting glucose
          • Urine dip
      • Consider
          • Urine PCR or ACR if dip positive or creatinine elevated (not done often enough)
          • Examining fundi (crucial if very high BP, optional otherwise)
          • An echo – not everyone needs one (recommended if abnormal ECG, murmur, elevated BNP or cardiac symptoms). Consider whether or not it will change management
          • CTCA and calcium score (can improve risk stratification)
          • Genetic testing only if suspected rare monogenic cause
          • NT-Pro BNP
      • Consider checking for secondary causes / associations (usually indicated if HTN and aged <40, resistant HTN, signs/symptoms suggestive of secondary cause, or severe HTN)
          • Radio-femoral delay
          • Renal USS/doppler
          • Aldosterone-renin ratio
          • TFTs and consider other hormone tests if signs of endocrinopathy
          • Metanephrines
          • Symptoms of associated conditions eg OSA, phaeo, autoimmune disease
          • Check for causative meds – steroids, NSAIDs, OCP, stimulants
      • Consider 24-hour monitor – daytime average of > 14 readings
  • Calculate 10-year CV risk
      • Can use the Q-risk3 calculator – but not if already diagnosed with CAD, have familial hypercholesterolaemia, or are aged <25 or >84
      • Bear mind variables which affect risk but are not included in scoring systems – previous pregnancy-related complications (eg PET, gestational HTN), south Asian ethnicity, socio-economic deprivation, autoimmune inflammation, HIV, severe mental illness
      • Check coronary artery calcium score if available, as this is an additional predictor of CV risk

Consider age and stage

  • Stage 1 HTN: clinic BP >140/90 and ambulatory / home BP >135/85
      • Lifestyle advice first
      • Consider drugs if target organ damage, comorbidities (CKD, DM, CVD) or 10-year CV risk >10%
  • Stage 2 HTN: clinic BP >160/100 and ambulatory/home BP > 150/95
      • Offer drugs and lifestyle advice
  • Stage 3 HTN: clinic BP >180/120 (meets criteria if either systolic or diastolic value over value stated)
      • Assess for target organ damage
      • If present, can start treatment immediately
      • If not, recheck BP in 7 days or monitor BP at home
      • Refer for same day specialist review if severe HTN, retinal haemorrhage, papilloedema, life threatening symptoms, suspected pheochromocytoma
  • If aged > 80
      • Some suggest having a higher threshold for starting medication (and only consider drugs if BP >150/90)
      • However, if not moderately or severely frail, might follow same guidance as for younger patients
      • Frailty is associated with a decrease in BP – the so-called BP J curve
      • Few trials have included patients in this age category
      • Avoid alpha blockers – more strongly associated with a postural drop
  • If aged < 40
      • Consider that 10-year CV risk will be low but lifetime risk high.
      • Screen for secondary causes
      • Ask about OCP use (consider switch to progesterone-only pill), recreational drugs and energy drinks
      • If obese – primary HTN still highly likely. But consider screening for OSA
  • If pregnant – see here

Lifestyle advice

  • Tends to be underemphasised
  • Consume < 5g salt per day
      • Reduces BP by 2-8mmHg (reduction is independent of baseline BP)
      • Reducing salt by 2.5g/day reduces CV risk by 20% (mostly through BP lowering effect)
      • There is a roughly linear relationship to salt intake and effect on BP (some evidence suggests that very low salt intake increase CV risk – a J curve – but this is may be due to bias in the data analysis)
      • Guidelines vary a bit but most suggest restricting salt to 5 or 6g/daily
      • Medications have more of an effect
      • WHO also advises >3.5g/day of potassium (unless advanced CKD, in which case restrict to <2.4g/daily). Effect on BP may be more pronounced in women. Can also eat potassium rich foods (spinach, avocado), or use potassium enriched salt (but not for old or pregnant people, those with DM, CKD, those taking ACEi- or ARBs)
  • < 14 units ETOH/week
      • Reduces BP by 2-4mmHg
      • Ingestion of ETOH decreases BP in the immediate term, and then increases BP after 12 hours (especially in men)
  • Modify diet
      • Increase vegetables, fruit, fish, nuts, grains, lean proteins, olive oil, low fat dairy.
      • Reduce red meat, Na, saturated/trans fats, sugar
      • DASH diet (dietary approaches to HTN) can reduce systolic by 8-14mm
      • Coffee is not generally associated with HTN (and may even be protective), but large amounts of caffeine from any source can contribute
  • Weight loss, aim BMI < 30
      • Reduces BP by 4.4/3.6 (sys/dia) mmHg per 5% body weight reduction
      • If BMI 40, weight loss of 13% is associated with 22% lower risk of HTN
      • GLP-1 receptor agonists also help reduced BP through weight reduction
  • Exercise 30 mins moderate exercise 5 x week
      • Reduces by 4-9mm systolic
      • Any exercise is good (except lifting very heavy weights which can be bad). Running and isometric exercises best (planks, glute bridge, squats etc)
      • ESC advise >30 minutes of moderate intensity on an average of 6 days per week, or 75 mins of high intensity over 3 days/week. Doubling this derives additional benefit
      • BP of >200/110 is a relative contraindication to high intensity exercise
  • Stop smoking

Overview of drug treatment for HTN

  • Guidance below is assuming non-pregnant / not considering pregnancy
  • Consider commencing medication immediately if > 160/100 (or if lower but high risk of CV disease)
  • Probably around 60% do not take medication as prescribed
  • Targets
      • Usually aim for < 140/90 if < 80yrs (<135/85 at home)
      • If borderline HTN (ie systolic 130-139) – have a lower threshold to treat with drugs if patient has established CV disease or an increased risk
      • Aim < 150/90 (<145/85 at home) if > 80 years (might avoid altogether if frail or limited life expectancy)
      • If postural drop – base target on standing BP
      • If BP lowering treatment not well tolerated – aim for as low as reasonably achievable
  • Monotherapy usually inadequate
      • If giving two drug combo, consider combined pill to increase adherence
      • Combining drugs early instead of increasing the dose of a single drug might be better – different drugs will tackle different mechanisms, and potentially lead to fewer side effects (ESC guidelines advise starting two drugs together for most patients)
      • Monotherapy might be better in borderline HTN, frailty, orthostatic HTN and age >85
  • All five main types of antihypertensives produce similar BP reductions
      • The average reduction in BP is 9/5.5 at standard dose and 7/4.5 at half dose (these are based on clinic readings. Probably less for ambulatory BP).
      • Three drugs at half standard dose will lead to around 20/11 reduction in BP
  • Relationship between drug dose and effect on BP is not linear
      • The magnitude of BP reduction with medications is partly based on the pre-treatment BP (Wilders principle)
      • ACE inhibitors in particular have a non-linear dose-response (ie. low doses are often inadequate). Higher doses tend to prolong duration of action rather than producing greater BP reduction
  • Most drugs take 1-2 weeks to impact BP significantly (so don’t follow up too early)
  • ARBs have longer action and better tolerability than ACE-I, but avoid both if planning pregnancy
  • May be best to use an ARB in preference to an ACEi in people of black African or African-Caribbean family origin
  • Betablockers are less effective at preventing CV events and especially stroke
      • So only use if another specific indication (eg angina, post-MI, CCF, arrythmias).
      • Also higher discontinuation rate due to side effects.
      • They do cause BP to fall by a similar amount as 1st line drugs however
  • If unsure about adherence vs resistant HTN – can check urine drug levels

Contraindications and side effects

  • Diuretics (best are Indapamide or Chlorthalidone)
      • Contraindications – gout, pregnancy, high calcium, low potassium, severe CKD
      • Side effects – less effective in CKD (although Chlorthalidone seems ok), increased urination, dehydration, hypokalaemia
  • Betablockers
      • Contraindications – athletes, asthma (if cardioselective, can use in low dose, if asthma not severe), AV block, arterial disease, isolated systolic HTN (as they increase stroke volume)
      • Side effects – fatigue, Raynaud’s, constipation, erectile dysfunction, bradycardia, worsening HF, reduced hypo awareness in DM
  • Calcium Channel Blockers
      • Contraindications – some tachyarrthymias, severe CCF
      • Side effects – Gingival hypertrophy (esp if poor oral hygiene, can switch to a newer CCB), reflux, bradycardia if rate-limiting
      • Ankle oedema can reflect efficacy and managed without stopping treatment. Diuretic won’t help. Advise to elevate legs, and can combine with ACEi or ARB
  • ACE-I and ARBs
      • Contraindications – pregnancy / planning pregnancy, hx of angioedema, high potassium, bilateral RAS
      • Side effects – dry cough for ACEi (switch to ARB), angioedema (<1%), AKI
  • Spironolactone
      • Contraindications – K+>4.5, acute/severe renal failure, Addisons
      • Side effects – hyperkalaemia, gynaecomastia
  • Alpha blockers
      • Contraindications – orthostatic hypotension, very prone to faints
      • Side effects – postural drop, headache, drowsiness
  • Combination of diuretics and betablockers increases risk of DM in those predisposed (eg pre-DM, hx of gestational DM)

The stepwise approach to pharmacological management

  • Always assess adherence, postural drop, and dosing, before considering treatment escalation
  • Step one
      • If < 55 years and not Afro-Caribbean – offer ACE-I or ARB (Ramipril 2.5-5mg, losartan 25mg OD)
      • If > 55 years or over, or Afro-Caribbean – offer a calcium-channel blocker eg amlodipine 5mg OD (If a CCB is not tolerated, for example, because of oedema, offer a thiazide-like diuretic, such as indapamide)
      • If diabetic any age – treat with ACE-I or ARB
      • If there is evidence of heart failure, offer a thiazide-like diuretic, such as indapamide 2.5mg OD
      • If starting / changing diuretic treatment for hypertension, offer a thiazide-like diuretic, such as indapamide, in preference to a conventional thiazide diuretic, such as Bendroflumethiazide
  • Step two
      • If hypertension is not controlled with step 1 treatment of an ACE inhibitor or ARB, offer a CCB or thiazide diuretic in addition
      • If hypertension is not controlled with step 1 treatment of a CCB, offer an ACE-I or ARB or a thiazide diuretic in addition
  • Step three
      • If hypertension is not controlled with step 2 treatment, offer a combination of an ACE inhibitor or ARB and a CCB, and a thiazide-like diuretic eg Indapamide
  • Step four
      • For people with a blood potassium level of 4.5 mmol/l or less (and eGFR >30), consider further diuretic therapy with low-dose spironolactone (25mg-50mg OD).
      • Use particular caution in people with a reduced estimated glomerular filtration rate because they have an increased risk of hyperkalaemia.
      • Eplerenone can also be used (but use at least 50mg BD) if anti-androgen side effects with spiro
      • Spironolactone can be increased to 300-400mg if necessary in primary hyperaldosteronism
      • If K+>4.5, consider a betablocker like Bisoprolol 5mg OD (although some guidelines suggest a more vasodilating betablocker like carvedilol, labetalol or nebivolol) if HR <70, or an alpha-blocker (Doxazosin 1mg OD) if K+ level higher and MRA contraindicated
      • Alpha blockers usually only recommended after betablockers and MRA have been used/considered
  • Step five
      • Often patients referred to hypertension clinics if taking at least 3 prescribed medications (resistant HTN), although clinics are oversubscribed and wait times can be long
      • Could add hydralazine 25mg TDS and titrate upwards
      • Can also use minoxidil (instead of hydralazine) but lots of side effects have been reported
      • Finerenone can be used in CKD with T2DM (better tolerated than spironolactone)
      • SGLT2 inhibitors cause modest BP drops
      • GLP1 agonists can be used in T2DM or for weight management, and will also help reduce BP
      • Aprocitentan – newly approved by NICE for resistant HTN. Endothelin receptor antagonist

New developments

  • Drugs
      • Aliskiren (a first in class renin inhibitor) has been withdrawn
      • Not many new drugs in last 20 years, however aldosterone synthase inhibitors (Baxdrostat) and angiotensinogen synthase inhibitors (Zilebesiran, 6 monthly s/c injection) might be coming
  • Pharmacogenetics
      • >1000 loci linked to BP control
      • Rare monogenetic forms exist eg salt sensitivity in Liddle’s syndrome
      • Polygenic risk scores may be helpful in the future
      • There is a differing response to drugs depending on genetics
  • Devices and procedures
      • Carotid barostimulation, endovascular baroreceptor amplification, iliac AV anastomosis – all fallen out of favour due to side effects
  • Catheter-based renal denervation
      • Can use radiofrequency, ultrasound or alcohol-mediated.
      • Quite safe. Requires femoral access however, which can cause complications.  0.25%–0.5% rate of renal artery stenosis/dissection requiring stenting
      • Modest reduction in BP in sham-controlled trials (less than or the same as a single drug), however quite individual and difficult to predict who will respond best. Likely to require ongoing drug treatment as well.
      • Consider in resistant HTN (ie on at least 3 drugs) or patient preference, particularly if adherence to medications challenging
      • Late complications may emerge, cost-effectiveness not proven, and research is ongoing.
      • Not advised if eGFR <40

Specific scenarios

  • HTN in CKD
      • Target BP often lower ie <130/80 (depends on the guideline)
      • ACE-I or ARB often 1st line (and can continue down to very low eGFR if K+ ok, or prescribe with K+ binder), but especially if proteinuric
      • Thiazide-like diuretics reduce BP down to eGFR <15
      • More detail here
  • Resistant HTN (15% of patients)
      • Defined as HTN despite multiple drugs (including a CCB, RAAS blocker and importantly a diuretic as excess salt intake and salt/water retention cause resistance to anti-hypertensives)
      • If eGFR<30 mL/min/1.73 m2 up-titrate loop diuretic
      • Check for postural drop and confirm at home or by ambulatory measurements (white coat HTN in differential)
      • Discuss adherence and consider combined pills. Ask in a non-judgmental way – sometimes people find it difficult, for many reasons, to take tablets every day. Does this happen to you?
      • Address lifestyle/behaviour – diet, exercise, salt, ETOH
      • Consider checking urinary compliance screen (majority non-adherent)
      • Seek expert advice if BP not controlled on optimal doses of 3 or 4 drugs
      • Consider secondary screen
      • Spironolactone is particularly useful as incidence of hyperaldosteronism in resistant HTN is around 20% (better than betablocker or alpha blocker). If renin levels very high, then the other options become more useful (but not worth measuring routinely). But avoid if K+ >4.5
  • Non-adherence
      • Adherence often poor (and reduces the more drugs someone is on)
      • Can be useful to check pharmacy prescription collection on GP record
      • Use caution if patient admitted with high BP and prescribed multiple drugs. Many report compliance but if they haven’t been adherent, starting multiple drugs will drop BP too fast (if concerned, check repeat prescriptions and look for clues. Can also check for urinary drug metabolites)
      • Can be improved with dosset boxes, apps, electronic prescribing, discussion, poly-pills
      • Ask about side effects of antihypertensives – cough (ACEi), dizziness, GI symptoms, fatigue, ankle swelling (CCB), erectile dysfunction (esp betablockers, centrally acting drugs and diuretics), gynaecomastia (MRAs)
      • Best to confirm non-adherence if suspected with urinary testing
  • Multiple drug intolerance
      • Often dose-dependent, so multiple drugs might be better than large doses of individual drugs
      • Consider other drugs (eg long-acting nitrates)
      • Consider renal denervation
  • Non-dipping nocturnal HTN
      • Can occur in sleep disorders incl OSA, high salt intake, orthostatic hypotension, autonomic dysfunction, CKD, DM, old age
      • There is a higher CV risk if BP doesn’t dip overnight (but nocturnal antihypertensive dosing doesn’t help)
  • Planning pregnancy
      • Refer to specialist clinic
  • Postural drop
      • Base target on their standing BP
      • Consider switching meds – might be best to avoid vasodilating betablockers, alpha blockers, hydralazine and minoxidil which can worsen postural drops
      • CCBs and ACEi/ARBs have less impact on postural BP (and if they do, usually in first 2 weeks of starting/increasing)
      • More intensive BP lowering treatment is not associated with an increased risk of postural hypotension (despite common opinion)
      • Consider additional contributors – neurodegenerative disease incl PD, DM, B12 deficiency, CKD, dehydration, deconditioning, other medications
      • Midodrine sometimes used if all else fails

 

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