Hypertension

Risk Factors

Age
Smoker
Dyslipidemia
Hx of Heart Disease in 1^st Degree Relative
Obesity
ATSI
Unsafe EtOH consumption
Familial hypercholesterolemia
Non-ischemic hear disease(AF, myopathy)
>75yeras
Sedentary Lifestyle

Causes/History

Essential 90-95%
Secondary

Kidney
- GN
- Reflux nephropathy
- Renovascular hypertension
  - renal artery stenosis
  - chronic kidney disease (diabetes, PCKD)
Endocrine
- Hyperthyrodism and Hypothyroidism
- Primary Hyperaldosteronism (Conns Syndrome)
- Hypercorticolism (Cushings disease)
- Phaechromocytoma
  - frequent headaches, sweating, palpitations
Coarctation of arota
Other
- Pregnancy
- Anemia
- Obstructive sleep apnoea
  - obesity, snoring, daytime sleepiness
- Immunological disorders – PAN
Meds
- OCPs, NSAIDs
- Clozapine
- steroids
- cyclosporine
- tacrolimus
- MAO-I
- SSRI/SNRI’s (venlafaxine, paroxetine, desvenlafaxine, reboxetine)
- Pseudoephedrine
- amphetamines (duramine)

In history identify

Modifiable lifestyle factors
- smoking, diet, weight control, obesity, exercise, recreational drug use, alcohol intake
Personal, psychosocial and environmental factors that could influence the effectiveness of antihypertensive care including:
- Education
- family situation
- work environment
- financial concerns, or associated psychological stress
- Depression
- social isolation and quality of social support

Category	Systolic	Diastolic
Grade 1	140-159	90-99
Grade 2	160-179	100-109
Grade 3	>180	>110
Isolated systolic	>140	<90
Isolated systolic with wide pulse pressure	>160	<70

Examination

Elevated blood pressure (usually the only abnormal sign)

Renal artery bruit.
Radiofemoral delay.
Cardiac examination:
- Left ventricular hypertrophy.
- Loud A2.
- Sinus tachycardia.
- Evidence of cardiac failure: basal crackles on lung auscultation, peripheral oedema, pulsatile liver.

Evidence of Arterial Disease:

Carotid, renal, abdominal or femoral bruits.
Abdominal aortic aneurysm.
Absent femoral pulses.
Radiofemoral delay.

Palpation:

Enlarged kidneys (e.g., polycystic kidneys).

Endocrine System Abnormalities:

Cushing’s syndrome.
Thyroid disease.

Obesity Assessment:

Waist circumference: measured in standing position midway between the lower border of the costal margin and uppermost border of the iliac crest.
Calculate BMI: body weight (kg) without shoes divided by height^2 (m^2).

Fundoscopy (Essential):

Keith-Wagener Classification:
- Grade 1: tortuosity of retinal arteries with silver wiring (↑ reflectiveness).
- Grade 2: Grade 1 + AV nipping.
- Grade 3: Grade 2 + flame-shaped haemorrhages and cotton wool exudates.
- Grade 4: Grade 3 + papilloedema.
Note: Grades 3 and 4 are diagnostic of malignant hypertension.

Investigations:

Urine dipstick

If abnormal/blood, send urine for microscopy.
Albuminuria and proteinuria status
- Highly recommended for all patients and mandatory for those with diabetes.
- Albuminuria and proteinuria can be measured using the ratio of concentrations to creatinine in urine, reagent strips
- If spot urine/ACR is in the macroalbuminuria range, a 24-hour protein level is recommended.
- Proteinuria is defined as >500 mg/day protein excretion rate.
- Urine PCR can be used for quantification and monitoring of proteinuria where albuminuria measures are not available.

BLOODS

BGL
Lipids, TG
Cr,Urea, eGFR
12-lead ECG

24 Ambulatory BP Monitoring

Suspected White-Coat Hypertension: including pregnancy.
Suspected Masked Hypertension: normal clinic BP, elevated ABP.
Suspected Nocturnal Hypertension or lack of nocturnal BP reduction (dipping).
Hypertension Despite Treatment.
High Cardiovascular Risk: even with normal clinic BP.
Suspected Episodic Hypertension.

Additional Uses:

Titrating antihypertensive therapy.
Borderline hypertension.
Early pregnancy hypertension.
Suspected/confirmed sleep apnea.
Syncope or orthostatic hypotension symptoms (not demonstrable in the clinic).

When Not Recommended:

No Specific Contraindications.
Not to Delay Treatment: in severe hypertension (clinic BP grade 3; systolic ≥180 mmHg, diastolic ≥110 mmHg).
Potential Inaccuracy: in irregular heart rate and arrhythmias

Interpreting Results:

Reference ‘normal’ ABP values for non-pregnant adults:
- 24-hour average: <115/75 mmHg (hypertension: ≥130/80 mmHg).
- Daytime (awake): <120/80 mmHg (hypertension: ≥135/85 mmHg).
- Nighttime (asleep): <105/65 mmHg (hypertension: ≥120/75 mmHg).
High Normal: ABP above normal but below hypertension thresholds.
Nighttime BP: should be at least 10% lower than daytime.
BP Load: <20% of readings exceeding hypertension threshold during 24 hours.
Other Metrics: BP variability, maximum systolic BP, morning BP surge.

Limitations:

Does not detect cardiac arrhythmias, may be inaccurate in atrial fibrillation.
Not designed for postural hypotension detection.
Diary data needed for positional and event-related information.

Special Investigations for Hypertension

Echocardiography:

Assess for left ventricular hypertrophy (LVH).

Carotid Doppler:

Evaluate for carotid artery disease.

Renal Artery Duplex:

Investigate for renal artery stenosis.

Peripheral Vascular Disease (PVD):

Ankle-Brachial Index (ABI).

Plasma Aldosterone/Renin Ratio:

Primary Aldosteronism:
- Occurs in 5–10% of hypertensive patients.
- Not excluded by normal serum potassium.
- Consider in moderate-to-severe or treatment-resistant hypertension, especially with hypokalaemia.
- Referral to a specialist for investigation is recommended.
- Interpretation is difficult in treated patients.

Cushing’s Syndrome Investigation:

Dexamethasone Suppression Test:
- Day 1:
  - 0900 hours: 5 mL blood for cortisol (optional baseline).
  - 2300 hours: give 1 mg dexamethasone orally.
- Day 2:
  - 0900 hours: 5 mL blood for cortisol.
- Normal result: cortisol < 50 nmol/L excludes Cushing’s syndrome.
- Failure to suppress indicates abnormal cortisol production (Cushing’s syndrome, endogenous depression, stress, obesity, chronic alcoholism, certain drugs like phenytoin).

24-Hour Urinary Free Cortisol:

Measure cortisol excretion over 24 hours.

Metanephrines and Catecholamines:

Indications: Symptoms of episodic catecholamine excess or episodic hypertension (suggestive of phaeochromocytoma).
Tests:
- 24-hour urinary metanephrine, normetanephrine, and catecholamines.
- Plasma metanephrine and normetanephrine concentration.

Obstructive Sleep Apnea (OSA) Investigation:

Epworth Sleepiness Scale.
STOP-BANG Questionnaire.
Sleep Study.

Specialist Referral:

Consider specialist referral for further evaluation and management in complex or refractory cases.

Non-Pharmacological Treatment

Reduce weight
- BMI < 25 kg/m2
- waist circumference
  - < 94 cm (men)
  - < 90 cm Asian males
  - < 80 cm (women) –1 mmHg per 1% reduction in weight
Reduce salt intake
- < 4 g/day of salt (approximately 1600 mg sodium) – 4–5 mmHg
- < 6g/day for primary prevention
Regular exercise
- Increase physical activity At least 30 min physical activity most days of the week – 4–9 mmHg
Modify diet
- Consume a diet rich in fruits, vegetables, and low fat dairy products and low in saturated and total fat – 8–14 mmHg
- Five serves of Vegetables and 2 serves of vegetables/day
Limit alcohol intake ≤ 2 standard drinks per day – 2–4 mmHg
Also, avoid smoking and treat hyperlipidaemia
Life scripts
- Write a script for Alocohol intake

Drug Treatment

Treatment initiation: Start therapy immediately if:

Grade 3 HT (>180/110)
isolated systolic and widened pulse pressure >160 / < 70
any evidence of end organ damage or associated conditions

Otherwise follow CVD risk calculator :

CVD risk assessment Eligiblity:

Adults ≥45 years of age
>35 years of age for Aboriginal and Torres Strait Islander peoples)
without a known history of CVD or other co-morbidities.

High (>15%)	start therapy
Mod (10-15%)	lifestyle modifications with 3-6 month follow up (recheck risk!!) and start if not at target (140/90)
Low (<10%)	lifestyle modifications with 6-12 month follow up (recheck risk!!) and if still low risk then start if BP > 150/90.

Hypertension: Identifying risk
Who is at risk?	What should be done?	How often?
Low absolute risk
<10% cardiovascular disease (CVD) risk	Provide lifestyle advice and education (I, B) Offer pharmacotherapy if blood pressure (BP) persistently over 160/100 mmHg Review BP of 140–159 mmHg after two months of lifestyle advice	BP every two years
Moderate risk
10–15% absolute CVD risk	Provide intensive lifestyle advice (II, B) Consider pharmacotherapy if systolic blood pressure (SBP) is 140–159 mmHg or diastolic blood pressure (DBP) is 90–99 mmHg. If SBP is 130–139 mmHg or DBP is 85–89 mmHg, review BP in six months ^{11, 36, 37, 41, 43} Offer pharmacotherapy simultaneously with lifestyle intervention if BP persistently over 160/100 mmHg or if family history of premature CVD or patient is of South Asian, Middle Eastern, Maori, Aboriginal, Torres Strait Islander or Pacific Islander descent (III, C)	BP every 6–12 months
High risk
>15% absolute CVD risk Clinically determined high risk: – diabetes and >60 years of age – diabetes with microalbuminuria (>20 μg/min or urine the urine albumin-to-creatinine ratio [UACR] >2.5 mg/mmol for males, >3.5 mg/mmol for females) – moderate or severe chronic kidney disease (CKD) (persistent proteinuria or estimated glomerular filtration rate [eGFR] >45 mL/min/1.73 m²) – previous diagnosis of familial hypercholesterolemia (FH) – SBP ≥180 mmHg or DBP ≥110 mmHg – serum total cholesterol >7.5 mmol/L – Aboriginal and Torres Strait Islander peoples aged >74 years – Existing CVD (previous event, symptomatic CVD), stroke or transient ischaemic attacks (TIAs) or CKD	Provide intensive lifestyle advice (II, B) ³ Commence pharmacotherapy (simultaneously with lipid therapy unless contraindicated) Treatment goal is BP ≤140/90 mmHg in adults without CVD, or lower (SBP <120 mmHg) in some individuals who tolerate more intensive treatment, and those with CKD (I, B to III, D;* ≤130/80 mmHg in people with diabetes or microalbuminuria or macroalbuminuria UACR ≥2.5 mg/mmol in males and >3.5 mg/mmol in females)	BP every 6–12 weeks
Existing CVD (previous event, symptomatic CVD), stroke or transient ischaemic attacks (TIAs) or CKD	Provide lifestyle risk factor counselling and commence pharmacotherapy to lower risk (I, A). There is some evidence that a treatment goal (SBP <120 mmHg) in some individuals who tolerate more intensive treatment provides additional benefit. Adverse effects need to be monitored ^43,46	Every six months
D recommendation for clinically determined high risk BP, blood pressure; CKD, chronic kidney disease; CVD, cardiovascular disease; DBP, diastolic blood pressure; eGFR, estimated glomerular filtration rate; FH, familial hypercholesterolaemia; SBP, systolic blood pressure; TIA, transient ischaemic attack; UACR, urine albumin-to-creatinine ratio*

MEDICATIONS

ACE inhibitors

Block the conversion of angiotensin I to angiotensin II (a potent vasoconstrictor)
Also block the degradation of bradykinin (a potent vasodilator)
Generally safe and effective.
Often first line
Particularly useful in:
- diabetics with nephropathy
- diabetics with depressed left ventricular function
- anyone with proteinuria
Side-effects are
- Profound hypotension following the fist dose
- Deterioration of renal function (in those with critical renovascular disease)
- Chronic dry cough (due to bradykinin)
- Hyperkalaemia (risk increased by rena impairment)
- Renal impairment (risk increased by hypovolaemia or NSAIDs)
- Angioedema (infrequent; may occur after years of treatment)
Contraindications
- Pregnancy
- Angioedema
- Hyperkalaemia
- Bilateral Renal aa Stenosis
MEDS
- Captopril 12.5–50mg twice daily
- Enalapril 5–40 mg daily in one or two doses
- Fosinopril 10–40 mg once daily
- Lisinopril 5–40 mg once daily
- Perindopril arginine 5–10mg once daily
- Perindopril erbumine 4–8mg once daily
- Quinapril 5–40 mg daily in one or two doses
- Ramipril 2.5–10 mg daily in one or two doses
- Trandolapril 1–4 mg once daily

Calcium channel blockers

Reduce blood pressure by causing arteriolar dilatation and some also reduce the force of cardiac contraction.
Like the β-blockers, they are especially useful in patients with concomitant ischaemic heart disease.
Lower initiating doses are clinically appropriate in some settings to maximise tolerability.
Long-acting (once daily) products are preferred.
Minimal effect on myocardial contractility and cardiac conduction.
Do not treat calcium channel blocker induced peripheral oedema with diuretics
Contraindications
- nil
Side effects
- Peripheral vasodilation
  - peripheral oedema
  - flushing
  - headache
  - dizziness
- postural hypotension
- tachycardia
- palpitations
- chest pain
- gingival hyperplasia flushing

Dihydropyridine calcium channel blockers
- Amlodipine 2.5–10 mg once daily
- Felodipine CR, 5–20 mg once daily
- Lercanidipine 10–20 mg once daily
- Nifedipine 10–40 mg twice daily
- CR, 20–120 mg once daily

(non-dihydropyridine) calcium channel blockers
- Less peripheral vasodilation than dihydropyridines.
- Reduce heart rate and depress cardiac contractility (verapamil more than diltiazem).
- Selected adverse effects:
  - Bradycardia, constipation (particularly verapamil, may be severe)
  - Atrioventricular block
  - heart failure
- Diltiazem CR, 180–360 mg once daily
- Verapamil
  - 80–160 mg two or three times daily
  - CR, tablet 180–480 mg daily
  - If >240 mg give in two doses CR capsule 160–480mg daily

β-Blockers

Reduce force of cardiac contraction, some reduce renin secretion and some reduce anxiety
When stopping, Stop beta-blockers slowly over >2 weeks to avoid problems, e.g. rebound hypertension, myocardial infarction
Major side effects of this class are
- Bradycardia
- Bronchospasm
- cold extremities
- fatigue
- bad dreams and hallucinations
Contraindications
- Asthma
- Bradycardia
- AV block – grade 2-3
- Uncontrolled Heart Failure
Especially useful in patients with both hypertension and angina
Eg:
- Atenolol 25–100 mg daily in one or two doses
  - not recommended monotherapy (poor outcomes in meta-analysis); consider changing if current monotherapy.
- Carvedilol 12.5–50 mg daily in one or two doses
- Labetalol 100–400 mg twice daily
- Metoprolol 50–100 mg once or twice daily
- CR 23.75–190 mg once daily
- Nebivolol 5 mg once daily
- Oxprenolol 40–160 mg twice daily
- Pindolol 10–30 mg daily in two or three doses
- Propranolol 40–320 mg daily in two or three doses

Diuretics

Thiazides
- Contraindications
  - GOUT
- The major concern is their
  - Selected adverse effects:
    - Postural hypotension
    - Dizziness
    - Hypokalaemia
    - Hyponatraemia
    - Adverse metabolic effects (↑ serum cholesterol, impaired glucose tolerance, hyperuricaemia and hypokalaemia)
- Eg:
  - Hydrochlorothiazide 25 mg once daily
  - Indapamide 1.5 mg once daily. CR, 1.5 mg has similar antihypertensive effect to 2.5 mg tablet but lower risk of hypokalaemia

Loop diuretics (frusemide)

Not recommended as an antihypertensive unless volume overload is present

Potassium-sparing
- Spirinolactone
  - aldosterone antagonist
  - Reduces potassium excretion
  - For treatment of
    - Blood pressure control – 12.5–50 mg
    - Primary hyperaldosteronism: 50–200 mg daily in one or two doses
    - Heart failure 25–50 mg once daily
  - Effective as add-on therapy in patients with resistant hypertension.
  - adverse effects:
    - Hyperkalaemia (risk increased by renal impairment)
    - hyponatraemia
    - Anti-androgenic effects (eg. mastalgia, gynaecomastia, sexual dysfunction)
- Aamiloride
  - Not effective when used alone
  - Contraindications: Hyperkalemia

Angeiotensin II antagonists

Share many of the actions of ACE inhibitors, but since they do not have any effect on bradykinin, do not cause a cough.
Currently used for patients who cannot tolerate ACE inhibitors because of persistent cough.
Contraindications
- Pregnancy
- Angioedema
- Hyperkalaemia
- Bilateral Renal aa Stenosis
Selected adverse effects:
- Hyperkalaemia (risk increased by renal impairment)
- Renal impairment (risk increased by hypovolaemia or NSAIDs)
- Cough and angioedema are rare
E.g.
- Candesartan 8–32 mg once daily
- Eprosartan 400–600 mg once daily
- Irbesartan 150–300 mg once daily
- Losartan 50–100 mg once daily
- Olmesartan 20–40 mg once daily
- Telmisartan 40–80 mg once daily
- Valsartan 80–320 mg once daily

α-blockers

Cause postsynaptic α₁blockade with resulting vasodilation and blood pressure reduction
Eg: Prazosin
- Initially 0.5 mg twice daily for 3–7 days.
- Maintenance, 3–20 mg daily in two or three doses
Reduce risk of first-dose hypotension by starting at night in low dose.
Before starting consider withholding diuretics and reducing dose of beta-blockers or calcium channel blockers.
Selected adverse effects:
- Hypotension (first-dose and postural), may be profound

Other vasodilators

Hydralazine

peripheral, mostly arteriolar, vasodilator
50–100 mg daily in two doses
Note: Used for refractory hypertension usually with a beta-blocker and diuretic.
Selected adverse effects:
- Palpitations
- Flushing
- Headache
- oedema
- Tachycardia
- may exacerbate angina (prevent reflex tachycardia by using with a beta-blocker or verapamil)
- Lupus-like syndrome (risk increased by doses >100 mg daily for >6 months)

Centrally acting drugs

Moxonidine
- centrally acting imidazoline agonist with minor alpha2 agonist activity
- 200–600 mcg daily in one or two doses.
- Maximum single dose is 400 mcg
- When stopping, withdraw over a few days.
- Maximum single dose is 400 mcg. Only 400 mcg and 200 mcg tablets are available in
- Australia.
- Selected adverse effects:
  - Dry mouth
  - CNS effects (e.g. somnolence, dizziness)
  - Bradycardia
  - Vasodilation

Methyldopa
- centrally acting alpha2 agonist
- 250–2000 mg daily in two to four doses
- Note: Predominately used for hypertension in pregnancy
- Limit use in other patients.
- Adverse effects limit use (except in pregnancy).
- Selected adverse effects:
  - CNS effects (e.g. sedation, dizziness)
  - hepatitis
  - hepatic necrosis
  - positive Coombs test
  - haemolytic anaemia

Clonidine
- centrally acting alpha2 and imidazoline agonist
- Initially 50–100 mcg twice daily, increase every 2–3 days.
- Maintenance 150–300 mcg twice daily
- Note: When stopping, avoid severe rebound hypertension by reducing dose over >7 days.
- Selected adverse effects:
  - Postural hypotension
  - Constipation
  - bradycardia,
  - dry mouth
  - CNS effects (e.g. sedation, dizziness)

Drug selection

Treatment is normally commenced with a single agent (monotherapy)
The most appropriate first-line agent will depend on
- Age
- Ethnic background
- Sex
- Concomitant illnesses
Thiazides and β-blockers have been used as first-line conventionally
More patients are now being prescribed ACE inhibitors as first line (an Ca-channel antagonists)
If monotherapy is unsuccessful, it is appropriate to move to combination therapy and certain combinations have been found to be particularly effective
- ACE inhibitor or β-blocker + diuretic
- Calcium antagonist + β-blocker

Prognosis

Depends on
- Level of BP
- Presence of target organ changes (retinal, renal, cardiac or vascular)
- Coexisting risk factors for cardiovascular disease
- Age at presentation
In general, treatment reduces the risk of stroke dramatically, and of coronary artery disease to a lesser extent.

Avoid :

ACEi/ ARB + K+ sparing diuretic – Hyper K+
ACEi/ ARB + NSAIDs + diruetics – ‘triple whammy‘ = Renal Failure
B- blocker + verapamil – Heart Block
Acei + ARB – does not reduce CVD death or morbidity and increases risk of hypotension, syncope and renal dysfunction.

Targets:

Patient Group	Target	Ambulatory BP equivalent	24hr	Night	Day
Uncomplicated Hypertension	140/ 90		133/84	121/76	136/87
People w CAD, DM, CRF, Proteinuria >300mg/day, Stroke/TIAend organ damageATSI	130/80		125/76	112/67	128/78

Strategies to maximise adherence to treatment plan

Communication
- Express empathy.
- Treat patient as a partner in management decisions.
- Assess patient’s expectations of treatment.
- At each visit, ask the patient, “Do you recall not having taken your medicines over the last four weeks?”
- Discuss consequences of non-adherence(i.e. stroke, accelerated hypertension).

Tailoring advice
- Discuss treatment options and agree on an initial plan.
- Provide specific, written instructions and education materials.
- Involve the patient’s family or carer in the management plan.
- Use self-measurement of blood pressure for monitoring, where appropriate.
- Consider referral for a Home Medicines Review.
- Evaluate the social and economic barriers that may affect medication supply and storage.
- Ensure the patient accepts the possibility of their specific therapy’s side effects.

Maintaining motivation
- Explain the risks and benefits of treatment, and risks of not treating.
- Clearly explain that drug treatment may be lifelong.
- Reassure the patient about their prognosis and the ability to lead a normal life.
- Address quality of life issues including any new symptoms or side effects of treatment.
- Address psychosocial factors that may limit adherence (i.e. manage depression if present*).
- Reinforce lifestyle advice at follow-up visits.
- Establish a long-term relationship between the patient and practitioner.

Increase Drug resistance

Causes: Lifestyle and diet
- Obesity.
- Physical inactivity.
- A diet high in salt.
- Heavy alcohol intake.
Drugs and medications
- NSAIDs (nonsteroidal anti-inflammatory drugs) like ibuprofen and naproxen.
- Nasal decongestants.
- Oral contraceptives (birth control pills).
Secondary causes
- Primary hyperaldosteronism, an excessive production of certain hormones from the adrenal glands.
- Renal artery stenosis, a narrowing of the arteries of the kidneys.
- Chronic kidney disease.
- Sleep apnea.
- Less common causes include pheochromocytoma, a tumor in the adrenal gland; aortic narrowing; and Cushing syndrome, an overproduction of some steroid hormones.

Hypertension

Causes/History

In history identify

Examination