CARDIOLOGY

COMPILED BY: ADAM VAUGHAN

LATEST UPDATE: JANUARY

2019
TABLE OF CONTENTS

Background........................................................................................................................................................................... 2

Chest Pain Differential Diagnoses.......................................................................................................................................... 3

SOB Differential Diagnoses.................................................................................................................................................... 3

Angina.................................................................................................................................................................................. 4

Atrial Fibrillation................................................................................................................................................................... 4

Palpitations.......................................................................................................................................................................... 4

Aneurysm............................................................................................................................................................................. 5

Ischaemic Heart Disease........................................................................................................................................................ 5

Cardiac Syncope and Sudden Death....................................................................................................................................... 6

Valvular Heart Disease.......................................................................................................................................................... 7

Heart Failure......................................................................................................................................................................... 9

Hypertension...................................................................................................................................................................... 11

Vascular Medicine............................................................................................................................................................... 14

Peripheral Arterial/Vascular Disease................................................................................................................................... 15

Dyslipidaemias.................................................................................................................................................................... 16

USEFUL RESOURCES
Oxford Handbook of Clinical Medicine
Wilkinson IB, Raine T, Wiles K, Goodhart A, Hall C, O'Neill H. Oxford Handbook of
Clinical Medicine. 10th ed.: Oxford University Press Inc; 2017.
Macleod’s Clinical Examination
Douglas G, Nicol F, Robertson C. Macleod's Clinical Examination. 13th ed.: Elsevier;
2013.
Kumar & Clarks’ Clinical Medicine
Kumar P, Clark M. Kumar & Clark's Clinical Medicine. 9th ed.: Elsevier; 2016.
 Background
HISTORY
Cardinal Symptoms Classical Presentations
 Chest pain  Chest pain – commonest symptom
 Oedema associated with IHD
 Palpitations  SOB – assess normal exercise
 Dizziness tolerance, associated symptoms and
 Breathlessness occurrence
o Dyspnoea – patient feels
Risk Factors breathless
 Age o Tachypnoea – ↑RR – evidence of
 Male SOB
 Hypertension
 Hyperlipidaemia COMMON CAUSES OF CLUBBING
 Diabetes  Cyanotic congenital heart disease
 Smoking  Infective endocarditis
 Family history of premature IHD  Lung carcinoma
(<60y/o) in a 1st degree relative  Lung abscess
 Peripheral vascular disease  Bronchiectasis
 Cerebrovascular disease  Empyema
 Previous angina/MI  Pulmonary fibrosis

Chest Pain Differential Diagnoses

ANGINA  Other features: restlessness, SOB,
feelings of impending doom, autonomic
 Central crushing chest pain – “heavy stimulation produces sweating, pallor,
weight, squeezing, pressure” – never diarrhoea and vomiting
sharp or stabbing
o Doesn’t change with position or
breathing
PERICARDITIS
 Sudden onset sharp/pleuritic chest pain
 Radiation: up to neck and down left
o Worse with coughing, inspiration,
arm (rare – down right arm, jaw,
swallowing and lying supine
epigastrium, back)
o Relived by sitting up and leaning
 Triggers: exertion, emotion,
forward
eating, extreme weathers
 Other features: ST elevation and
 Other features: palps, grey skin,
presence of “rub”
sweaty, SOB

MYOCARDIAL INFARCTION AORTIC DISSECTION

 10/10 tearing chest pain – can present
 Pain is more severe than angina
collapsed
o Lasts >20min, relieved by
 Radiates to back
rest, but GTN does not
help  Unequal BP between arms as different
branches of the aorta occlude – if
 dissection extends proximally, MI can  Pancreatitis – epigastric pain radiating
occur to back, vomiting, tachycardia,
hypotension
NON-CARDIAC CHEST PAIN  Gall stones – epigastric pain radiating
 PE – pleuritic chest pain, sudden onset, to shoulder, worse with fatty food
SOB, haemoptysis  Costochondritis – exacerbated by
 Pleurisy – sharp pain on inspiration, movement
with markers of infection  Strained intercostal – worse on
 Pneumothorax – dull persistent pain, inspiration, tender
SOB  Anxiety – SOB, tingling lips, stress
 Lung cancer – non-specific dull ache

SOB Differential Diagnoses

HEART FAILURE  ↑HR
 Sudden onset of SOB
 Orthopnoea – SOB caused by lying
flat – sleep in a chair
 Gallop rhythm
OTHER
 Angina
 Bilateral basal crepitations
 MI
 Apex beat in 6th intercostal space
 Myocardial ischaemia
 Pulmonary/peripheral oedema
 Arrhythmias
 PND
 Pericardial disease
VALVE DISEASE – AORTIC  Pulmonary disease
 Anaemia
STENOSIS  Obesity
 Symptoms – angina, dyspnoea,  Being unfit
dizziness, syncope (triad of HF,  Pancreatitis
angina, syncope)  PE
 Pneumothorax
ACUTE TAMPONADE  Asthma
 Becks triad: ↓BP, ↑JVP, muffled heart  Interstitial lung disease
sounds  Anxiety

Angina
 Pain or discomfort in the chest due to
insufficient blood flow to the heart
INVESTIGATIONS
muscle  ECG
 Typical stable angina – pain, triggered  FBC, U&Es, thyroid, lipids, HbA1c
by exertion, relieved by rest or GTN
within 5mins MANAGEMENT
 Atypical angina – 2 of the above  GP presentation – refer to rapid
 Angina unlikely – 1 of the above access chest pain clinic
 Unstable angina – attacks are o If chest pain in last 72
unpredictable and can happen on hours – ECG then send to
minimal exertion hospital
o 999 if chest pain now
 Aspirin/Clopidogrel
  ACEI

Atrial Fibrillation
 Irregularly irregular pulse, usually fast – ECG has no P waves and irregular QRS
 Cardiac output drops by 20% as the ventricles aren’t reliably primed by the atria
 Can be asymptomatic or cause typical cardio symptoms
 Causes: HF, hypertension, MI, PE, pneumonia, mitral valve disease, hyperthyroidism,
caffeine, alcohol, post op, ↓K⁺, ↓Mg²⁺

MANAGEMENT
 Lower HR – digoxin, β blockers
 Make heart beat regular – anti-arrhythmic drugs – Ca²⁺ channel blockers, β blockers
 Cardioversion if new case or young
 Stroke prevention – warfarin, NOACs
 Ablation of accessory pathways

Palpitations
 Awareness of the heart beating
 Causes: anaemia, arrhythmia, hyperthyroidism, anxiety, smoking, caffeine, alcohol,
exertion, drugs
 Red flags: SOB, pain, LOC

INVESTIGATIONS
 24h ECG
 FBC, thyroid, U&Es, lipids, HBA1C

Aneurysm
 Dilation of 3-3.5cm = aneurysm
o Operate at 5.5cm diameter
 Strong popliteal pulse could be a popliteal aneurysm
 AAAs are expansile
o Pulsatile masses can be structures overlying the aorta instead of the aorta itself
 Ischaemic Heart Disease
Stable Unstable
Angina Angina NSTEMI STEMI

Increasing Atherosclerosis and Blockage

A C
CUTE ORONARY YNDROME S o Don’t use response to GTN to
make a diagnosis
(ACS)  GRACE score used as ACS risk model –
 All IHDs apart from stable angina shows chance of death or death/MI in
 Indicates that something will get worse hospital and in the next 6m
soon Enzyme Rise – Troponin T
 To classify as ACS, patients must have >2  Not found in serum of healthy
of: people; after myocardial injury, it
o Cardiac chest pain leaks into serum
o Dynamic ECG changes o Troponin can also be elevated
o Significant change in troponin in PE, sepsis, post-op, AF, LVF
(±20%)  Maximum sensitivity is at 12-24h after
 Symptoms: central chest pain lasting onset
>20mins, nausea, sweating, o High enough to be detected
dyspnoea, palpitations, pallor, signs an hour after chest pain
of heart failure o May get false negative if take
blood too early
DIAGNOSIS  ↑ Troponin = ↑ death risk
 At least 2 of: chest pain, elevated
troponin, ischaemic/necrotic ECG MI MANAGEMENT - MONAC
changes (ST elevation (tombstone R
 Morphine
waves), ST depression, T wave
 O₂
inversion, LBBB)
 Nitrates
 Aspirin
  Clopidogrel

QRISK CARDIOVASCULAR DISEASE RISK CALCULATOR

 Calculates chance of heart attack or stroke in next 10y
 If >10% 10y risk, give atorvastatin 20mg
 Don’t use QRISK if:
o Inherited disorders of lipid metabolism
o Pre-existing CVD
o Chronic kidney disease – eGFR <60
o Type 1 diabetes
o Age >85 – risk is due to age alone
 QRISK can underestimate risk in people: taking anti-hypertensive or lipid modification
therapy, treated for HIV, taking medications that cause dyslipidaemia (antipsychotics,
corticosteroids, immunosuppressants), with autoimmune disorders, with a BMI >40,
triglycerides >4.5

Numbers Needed to Treat (NNT)

 NNT = the number of patients you need to treat to prevent one bad outcome
 To calculate NNT, you need to know the absolute risk reduction (ARR)
o ARR = CER (control event rate) – EER (experimental event rate)
 NNT is the inverse of ARR
o NTT = 1/ARR

Cardiac Syncope and Sudden Death

 A death is sudden if it occurs within 1h of the onset of symptoms
 Commonest cause of sudden death in the UK is ischaemic heart disease
 History: sudden collapse, no prodrome, rapid recovery, seizure activity, prev cardiac
problems, FH
o Blackout with exercise or startle reflex → long QT syndrome
o Blackout with pain, stress, adrenaline → catecholinergic polymorphic VT in
children/teens
 Signs: any signs of HF/LV dysfunction, carotid sinus hypersensitivity, ECG abnormalities
 Investigations: ECG, echo, heart monitors, genetic testing
o Heart monitors: Holter ECG (1-7d), Zio patch (14d), Memo, implantable loop recorder
 ECG changes: Q waves, heart block, bifascicular or trifascicular block, delta waves, epsilon
waves

ARRHYTHMOGENIC RIGHT VENTRICULAR CARDIOMYOPATHY

(ARVC)
 Common in athletes – autosomal dominant inheritance
 RV myocardium is replaced with fibro-fatty material
o Mutation of desmosomes makes them weak and break as the heart stretches
 ECG shows RBBB, T wave inversion and broad QRS in v1-3, epsilon wave in V1

LONG QT SYNDROME
 Causes polymorphic VT
 Prolonged repolarisation due to problem with K⁺ channels
  Causes: congenital (autosomal dominant), MI, mitral valve prolapse, HIV, ↓K⁺, ↓Mg²⁺, ↓Ca²⁺

SHORT QT SYNDROME
 Quick repolarisation due to problem with K⁺ channels
 Short QT not changing with HR, tall T waves, heart is structurally normal
 Autosomal dominant inheritance

BRUGADA SYNDROME
 Causes ventricular arrhythmia
 Coved ST elevation in V1-3 due to Na⁺ channel problem
 ECG changes can be precipitated by fever, medications, electrolyte imbalance and ischaemia
 Autosomal dominant inheritance

CATECHOLINERGIC POLYMORPHIC VENTRICULAR TACHYCARDIA

(CPVT)
 Bidirectional VT or VF during stress or exercise
 Problem with Ca²⁺ channels

CHANNELOPATHIES
 Channelopathies cause cardiac arrest as all cells fire and reset at different times,
leading to polymorphic VT or VF
o Polymorphic VT is usually due to drugs, toxins or genetics

CARDIOMYOPATHIES
 Cardiomyopathies cause cardiac arrest as they cause increased turbulence, leading to
monomorphic VT and VF – “rocks in a river causes turbulence”
o Hypertrophic cardiomyopathy alters the grain of the myocardium due to tangles
o In ARVC, clusters of fat and fibrous tissue are deposited between cells in
response to stretch damage – worsens with exercise
o In dilated cardiomyopathy (DCM) and post infarcted hearts, the chamber dilates
and scars form due to an actual scar of the infarct or a poisoning process (from
long term adrenaline, ACE and aldosterone) – conduction in scar tissue is slow

Valvular Heart Disease

 Stenosis – narrowing and obstructing  Regurgitant lesions produce a volume
 Regurgitation – leaky valve overload ventricle with resulting
 Valve pathology produces a murmur dilatation
due to turbulent flow  All left sided valve lesions produce
o Murmurs can also be heard with pulmonary hypertension due to
normal valves in high flow elevated left atrial pressure
situations, but are always
systolic: pregnancy, anaemia, PHYSIOLOGY OF VALVE
pyrexia
 Stenotic valve lesions create problems
FUNCTION
with pressure overload in the chamber  When LV pressure rises above aortic
before the stenosis – heart has to work pressure, aortic valve opens
harder to open the valve  When LV pressure falls below aortic
o Aortic stenosis → LV hypertrophy pressure, aortic valve shuts – sound S2
o Mitral stenosis → LA dilatation  When LV pressure rises above LA
pressure, mitral valve opens
  When LV pressure falls below LA
pressure, mitral valve shuts – sound S1

TYPES OF VALVE DISEASE

Degenerative Aortic Valve Disease Congenital Valve Disease
 Normal valve → sclerosis →  Bicuspid aortic valve – 2 leaflets
calcification instead of 3 – more prone to
o Valve leaflets become stiffer degeneration
and more difficult to open
Endocarditis
Rheumatic Valve Disease  Vegetation on valves
 Valves thicken and edges of leaflets
fuse so opening is just a slit

SYSTOLIC MURMURS
 Aortic stenosis – valve open in systole
o LV pressure is increased as the heart has to work harder to push blood through
the narrowed valve → LV hypertrophy
o It takes longer for the valve to open to its maximum – can be detected as a slow
rise in arterial pulse and a narrow pulse pressure
o Produces a crescendo/decrescendo systolic murmur as the valve opens and
closes slowly – starts just after S1
 Mitral regurgitation – valve closed in systole
o Blood leaks back so a murmur can be heard the whole time the valve is closed
o Produces a pansystolic murmur – starts with S1 and lasts until S2
 In mitral valve prolapse, the leaflets briefly come together, but then one buckles back
and leaks
o Murmur is heard just after S1 and begins with a click as the valve buckles

DIASTOLIC MURMURS
 Aortic regurgitation – valve closed in diastole
o Pressure in the aorta drops quickly in diastole (leak acts as a slow puncture) so
the LV has to shift blood that has leaked back, so LV pressure increases
o Produces an early diastolic murmur – louder in early diastole and quietens as
pressures equalise
 Hard to hear – listen with diaphragm at lower left sternal edge and lean
patient forward and hold breath in expiration – this moves the heart to
the front of the chest
o The more severe the regurgitation, the more rapidly pressures equalise and the
shorter the murmur
o Gives a wide pulse pressure (difference between systolic and diastolic
pressures) and a collapsing pulse

 Mitral stenosis – valve open in diastole

o Produces a low pitched, rumbling, mid-diastolic murmur – starts just after S2
and lasts until S1
 Presystolic accentuation in sinus rhythm due to LA contraction
 Hard to hear – listen with bell on the apex beat and roll the patient to left
and hold breath in expiration
 o Most patients with mitral stenosis are in AF
o Clinical features: malar flush, AF, tapping apex beat – palpable S1, loud S1 with
opening snap and mid-diastolic murmur

HEART SOUNDS
 S1 – closure of mitral and tricuspid valves – in time with pulse
o Loud S1 = mitral stenosis – ventricular filling is limited so instead of a gradual
decrease in flow and slow closing valve, the valve shuts rapidly as blood travels
through the valve for longer at its max flow
o Soft S1 = mitral incompetence (valve fails to snap shut) or prolonged filling
time
 S2 – closure of aortic and pulmonary valves
o Loud S1 = hypertension
o Soft S1 = aortic stenosis

MURMUR SUMMARY
 Ejection systolic murmur = aortic/pulmonary stenosis
o Heard between S1 and S2 as a crescendo/decrescendo
o Radiates to carotids
 Pansystolic murmur = mitral/tricuspid regurgitation or ventricular septal defect
o Heard between S1 and S2 as a solid whoosh
o Radiates to axilla
 Early diastolic murmur = aortic/pulmonary regurgitation
o Heard after S2 as “absence of silence” – high pitch
 Mid-diastolic murmur = mitral stenosis or aortic regurgitation
o Heard after S2 as a low pitched rumble
 Accentuating manoeuvres
o Expiration – left sided murmurs
o Inspiration – right sided murmurs
o Leaning forward – aortic regurgitation
o Rolling left – mitral stenosis
 Thrills – palpable murmurs
 Heaves – right ventricular enlargement
 Heart Failure
 Inability of the heart to supply sufficient blood to body tissues
 Tissue hypoperfusion → fatigue, ↓exercise capacity, renal dysfunction
 Fluid congestion → oedema, dyspnoea, hepatic dysfunction, bloating
 The heart fails some time after a MI due to LV remodelling and worsening cardiac
functioning, as well as neurohumoral activation which causes ↑TPR and remodelling
o Neurohumoral activation is ideal in the short term to protect against blood loss
(↑BP to preserve perfusion), but harmful long term (↑afterload, ↓SV, Na⁺
retention, necrosis)
 Clinical features: cyanosis, ↓BP, narrow pulse pressure, pulsus alternans, displaces
apex, RV heave
 Investigations: ECG, echocardiography to show dysfunction and valve disease, B-
natriuretic peptide is raised, CXR, FBC, U&E

New York Classification of Heart Failure

1. No dyspnoea from normal activity
2. Comfortable at rest, dyspnoea from normal activity – mildly limiting
3. Less than normal activity causes dyspnoea – moderately limiting
4. Dyspnoea at rest, all activity causes discomfort – severely limiting

TYPES OF HF
 Systolic failure – ventricle is unable to  RV failure
contract normally = ↓cardiac output o Peripheral pitting oedema,
o EF <40% ascites, nausea, anorexia,
o Causes: IHD, MI, epistaxis
cardiomyopathy  Low output HF – cardiac output is low
 Diastolic failure – ventricle is unable to and does not increase with exertion
relax and fill = ↑filling pressure o Causes: excessive preload
o EF is preserved (mitral regurg), pump failure
o Causes: ventricular hypertrophy, (HF, ↓HR, -ve ionotropic drugs),
constrictive pericarditis, chronic excessive afterload
tamponade, restrictive (aortic stenosis, hypertension)
cardiomyopathy, obesity  High output HF – occurs when
 LV failure demands are increased so much that
o Central oedema → PND, the heart can't cope
orthopnoea, fatigue, weight loss, o Causes: anaemia, pregnancy,
wheeze hyperthyroidism, A-V shunting

MANAGEMENT
Chronic HF o Increase diuretic dose or use
 Maintain euvolaemia (i.e. stop fluid IV route
build-up) o Combine a loop and thiazide
 Diuretics – Furosemide diuretic – furosemide +
 Anticoagulation bendroflumethazide
 Stop smoking, alcohol, salt o Dobutamine infusion if very
 Annual flu vaccine, one-off resistant
pneumococcal vaccine  Aims of treatment: symptom relief
 If treatment resistance occurs (↓SOB, ↓fluid retention), survival
o Salt and fluid restriction benefit
o DVT prophylaxis – tinzaparin
Acute HF  When stable, start β blockers, ACEI,
 Sit patient up to reduce venous or aldosterone agonist (in that
return and reduce heart preload order)
 O2 to maintain sats
Device Therapy for HF
 IV diamorphine – 1.25-5mg
 Implantable cardioverter defibrillator
 IV furosemide – 40-80mg – shifts
(ICD)
fluid out of lungs
 Biventricular pacemakers – cardiac
 GTN if systolic BP >140
resynchronisation therapy (CRT-P)
 Combined devices (CRT-D)

DRUG TREATMENTS
Lisinopril, Cough, renal impairment, hyperkalaemia,
Beneficial for HF

ACEI
Ramipril hypotension, angioedema
Angiotensi
Renal impairment, hyperkalaemia,
n II Losartan
hypotension
antagonists
Chronic HF

Bradyarrhythmias, cold extremities,

Atenolol,
Β blockers bronchospasm, fatigue, worsening HF,
metoprolol
intermittent claudication
Spironolacto
K⁺ sparing
ne, Hyperkalaemia, gynaecomastia
diuretics
amiloride
Digoxin toxicity - nausea, vomiting, abdo
Cardiac
Digoxin pain, confusion, brady and
glycosides
tachyarrhythmias
Urinary frequency, hypokalaemia, volume
Loop Furosemide,
depletion, renal impairment, gout, urinary
diuretics bumetanide
retention
Acute HF

Inotropes Dobutamine (Also used in cardiogenic shock)

Diamorphin
Opiates
e Useless for HF – used to control Sx
Nitrates GTN
 Hypertension
 Stage 1 HTN – clinic BP >140/90 + ABPM or HBPM average >135/85
o Lifestyle changes and arrange a 24h monitor
 Stage 2 HTN – clinic BP >160/100 + ABPM or HBPM daytime average >150/95
o Urgent 24h monitor – treat BP
 Severe HTN – clinic sBP >180 or dBP >110
o Treat immediately
 If clinic BP >140/90, offer ambulatory blood pressure monitoring (ABPM) to confirm the
diagnosis
 Causes: obesity, salt, ↓exercise, genetics, kidney disease, diabetes, obstructive sleep
apnoea, COCP, steroids (Conn’s), NSAIDs, “white coat”, pain, anxiety, cocaine, flu
remedies, cyclosporine, erythropoietin
 Complications: MI, stroke, hypertensive nephrosclerosis, dissecting aortic aneurysm,
peripheral vascular disease, silver wiring on ophthalmology, hypertensive
encephalopathy
 Accelerated (malignant) HTN
o Clinical features: headache, visual impairment, renal impairment, cardiac
failure, neuro signs, microangiopathic haemolytic anaemia, fundal changes
 Benefits of BP reduction – 38%↓ in stroke and 16% reduction in CHD
 Routine assessment examination: BP, BMI, pulses, palpate and auscultate kidneys
(palpable → ADPKD), U&E (protein:creatinine ratio to assess for renal failure),
urinalysis, ECG, fundoscopy

PATHOPHYSIOLOGY
 Reduced elasticity and compliance of large arteries – normal ageing
o HTN leads to ↑ accumulation of arterial Ca²⁺ and collagen and degradation of
elastin
o Stiff vessels increase rate of return of reflected pressure waves → increases sBP
 Defective Na⁺ storage leads to retention of fluid
 Inappropriate activation of the renin-angiotensin-sympathetic system
o Usually keeps BP high enough to perfuse the brain when standing up
1. ↓kidney perfusion makes kidney think blood vol and BP are low
2. Renin is released and converts angiotensinogen to angiotensin I
3. Angiotensin converting enzyme converts angiotensin I to angiotensin II
4. Angiotensin II causes vasoconstriction and aldosterone release
5. Aldosterone causes ↑Na⁺ channels in collecting duct = H₂O retention =
↑blood volume
 6. BP increases

AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE (ADPKD)

 Rare but important cause of renal disease leading to renal failure – presents with HTN

SECONDARY ENDOCRINE HYPERTENSION

 Catecholamine excess – phaeochromocytoma
 Glucocorticoid excess – Cushing’s syndrome
 Mineralocorticoid excess – Conn’s syndrome
 Aldosterone excess – shuttle enzyme deficiency
 Mimicking aldosterone excess (channelopathy) – Liddle’s syndrome
 GH excess – acromegaly

IMAGING FOR COMPLICATIONS

 Cerebrovascular disease
o If stroke, CT within an hour – MRI if delayed presentation
o CT if symptoms lasting >1h – MRI if symptoms last >14d
 Carotid imaging
o Used to screen patients who might benefit from CEA
o Carotid duplex US – non-invasive and safe
o CT angiography – contrast can damage kidneys

ACEI Ca²⁺ channel Diuretics β blockers

Lisinopril, Ramipril blocker Bendroflumethiazid atenolol, bisoprolol,
----------------------------- Amlodipine, e, chlortalidone propanolol
-- nifedipine --------------------------- ----------------------------------
Inhibits: AngI→AngII, ------------------------------ -- ---
bradykinin -- ↓ blood vol ↓ HR – slows conduction
breakdown, Block Ca²⁺ entry to ↓ peripheral in atria and AV node
aldosterone SM cells → resistance ↓ contractility
secretion vasodilation --------------------------- ↓ peripheral resistance
Renal vasodilation ↓ contractility -- Inhibits RAS
----------------------------- ↓ HR Indications: heart ----------------------------------
--- ------------------------------ failure, elderly + ---
Indications: heart -- ISH Indications: angina, post
failure, LV Indications: elderly + Contraindications: MI, tachycardia, heart
dysfunction, post MI, ISH, angina gout, renal failure, ? failure, pregnancy,
diabetic Contraindications: R diabetes, ? diabetes
nephropathy, renal sided heart failure hyperlipidaemia, ? Contraindications:
impairment sexually active Asthma, COPD, heart
Contraindications: males block, ?hyperlipidaemia, ?
pregnancy, If dry physically active, ?PVD
hyperkalaemia, renal
cough If ankle
artery stenosis, PVD
Angiotensin α blockers swelling Pregnancy >55 or
receptor blockers Doxazosin, prazosin Give: methyldopa, <55 Afro
(ARBs) ------------------------------ nifedipine, labetalol Caribbean
Losartan -- Avoid: β blockers, Ca²⁺
----------------------------- Block SM α₁ 1 ACEI
diuretics, ACEI blocker
--- adrenoceptors → Ca²⁺
Inhibits AngII vasodilation Non-drug 2 block ACEI
Vasodilation ↑HR treatment er
 “first dose ↓salt, ↓fat, ↓alcohol, 3 Diuretic
phenomenon” ↓BP ↑exercise, ↓stress 4 α/β blocker
------------------------------ Initiate treatment:
-- Target BP Stage 1 HTN + <80 +
Indications: age >80 = 150/90 evidence of organ
prostatism, glucose age <80 = 140/90 damage
intolerance
Stage 2 HTN + any age
Contraindications:
urinary incontinence,
orthostatic Refer for specialist
hypotension, elderly evaluation:
Stage 1 HTN + <40 +
no evidence of organ
damage
BP MANAGEMENT

Vascular Medicine
 Metabolic syndrome is a cluster of risk factors predisposing to CVD
o Insulin resistance, hyperinsulinaemia, impaired glucose tolerance, central
obesity, HTN, dyslipidaemia (↑triglycerides, ↓HDL)

ATHEROSCLEROSIS
 Atherosclerosis is the development of deposits of fibrous tissue and lipids on arterial
walls
 Effects of atherosclerosis: ischaemic heart disease, peripheral vascular disease, cerebrovascu
disease
 Cause is unknown, but there are many risk factors
 Risk factors: age, male, FH, hyperlipidaemia, HTN, smoking, diabetes, obesity,
genetics (chromosome 9p2 – CDKN2B-AS transcript)
 Arteries affected: diameter >1mm, sites of haemodynamic stress (bifurcations),
brachial arteries are spared

Types of Lesion
 Type I (initial) – isolated macrophage foam cells
  Type II (fatty streak) – intracellular lipid accumulation
o Slightly elevated zone on the arterial wall
 Type III (intermediate) – intracellular lipids and small
extracellular lipid pools
 Type IV (atheroma) – intracellular lipids and extracellular lipid
core
 Type V (fibroatheroma) – lipid core and fibrotic layer
o Lipid accumulates
o Fibrosis forms a cap over the lesion
o Smooth muscle cells migrate and proliferate
 Type VI (complicated) – surface defect, hematoma-haemorrhage,
thrombus
o Ulcers and fissures of the fibrous cap reveal plaque
contents, causing fibrosis
o The plaque can undergo calcification – visible on x-ray

Pathogenesis of Atherosclerosis
Lipid Hypothesis
 More LDL = more deposition
 HDL protects against atherosclerosis
Response to Injury Hypothesis
 Injury to the endothelium triggers monocyte adhesion, a loosening of endothelial cell
junctions, and migration of monocytes beneath the endothelium where they
differentiate into macrophages
 The more permeable endothelium allows LDL to enter the intima of the artery, and
macrophages begin engulfing the LDL by phagocytosis
 After macrophages become laden with lipid from ingesting LDL, they are referred to as
"foam cells," and collections of these create fatty streaks
 T-lymphocytes in the intima secrete cytokines that eventually induce smooth muscle
cells to migrate from the media to the intima
 These smooth muscle cells begin to proliferate under the influence of growth factors
 Over time there is a progressive accumulation of lipid and smooth muscle cells in the
intima, and eventually the growing lesion begins to raise the endothelium and
encroach on the lumen of the artery

Consequences of Atherosclerosis
 Luminal narrowing → ischaemia – chronic effects
 Luminal occlusion → infarction – acute effects
 Embolism → ischaemia and infarction
 Weakened wall → aneurysm
o Commonest site for aneurysm is the infrarenal abdominal aorta
o Patient with ruptured aneurysm presents with: severe abdo/back pain, shock
due to blood loss

 Heart problems
o Angina/MI due to narrowing of coronary arteries
 Brain problems
o TIA due to emboli (emboli usually lyse to leave no lasting deficit)
o Infarction due to occlusion of a cerebral artery
 Leg problems
o Pain due to atheroma of the femoral artery reducing blood supply to the lower
leg
  Pain in the calf when walking and relieved by rest – claudication
o Gangrene due to infarction of tissues served by a blocked artery
 Gut problems
o Ischaemic enteritis causes pain and bloody diarrhoea
 Kidney problems
o Hypertension due to blocked renal artery triggering kidney atrophy
 Under-perfused kidney releases renin

Peripheral Arterial/Vascular Disease

 Narrowed arteries reduce blood flow to limbs meaning the demand is not met
 Atherosclerosis is a systemic disease, it is just by chance where it presents clinically
first
 Symptoms: claudication, reduced hair growth, pale/blue skin, thick opaque toe nails,
ulcers and wounds that won’t heal
 Smoking is the most important risk factor
 Intermittent claudication – calf pain brought on by exercise and relieved by rest
 Critical limb ischaemia – rest pain, ulceration, necrosis
 Acute limb ischaemia – sudden compromise in blood supply to the limb
o 6Ps: pale, pulseless, paraesthesia, pain, paralysis, perishingly cold
 Diagnosis: Doppler ultrasound, CT angiogram, peripheral arterial angiogram, ABI
o Ankle-brachial index (ABI) – quantifies the severity of arterial occlusion in the
leg
 BP in legs compared to BP in arms – if lower in legs, arteries are blocked =
PAD
 False high readings can occur in diabetics whose arteries are non-
compressible
 >1 = normal
 <0.9 = impaired arterial supply – intermittent claudication
 <0.5 = severe arterial disease – rest pain
 <0.2 = gangrene, ulceration
 Management: anticoagulation, analgesia, embolectomy, thrombolysis, aspirin
(antiplatelet), statin (stabilises plaques), surgical revascularisation (endarterectomy,
bypass, angioplasty, stents)

Claudication
 Pain in leg muscles on walking due to insufficient blood supply
 Most commonly affects the calf
 Critical ischaemia/rest pain – worse outcome
o People with poor blood flow to the leg will not feel pain when upright as gravity
pulls blood down the legs, but once lying in bed, oxygen does not reach the
tissues due to the arterial narrowing
 Ask the patient how far they can walk before the pain comes on – claudication
distance
 Dyslipidaemias
 The higher the cholesterol in the blood, the higher the risk of cardiovascular disease
 50% of patients with premature CHD have a familial lipid disorder
 Severe hypertriglyceridaemia can cause acute pancreatitis
 Disorders of plasma lipid transport cause an increase in plasma lipid levels
 History: SOB, angina, claudication, thirst, polyuria, muscle/joint pain, smoking/alcohol,
diet
 Examination: BMI, waist circumference, eyes, Achilles and digital extensor tendons,
knees and elbows, palms and flexures, heart sounds, pulses, bruits, BP

TYPES OF LIPOPROTEIN
 LDL keeps its structure for the longest
 Lp(a) makes LDL more sticky to blood vessels – some people have it, some don’t
 HDL has functions in inflammation and combatting infection – doesn’t contribute to
atherosclerosis and cleans up cholesterol deposits
 Lipoproteins contributing to atherosclerosis the most: chylomicron remnants, IDL, LDL,
Lp(a)

BASIC SERUM LIPID MEASUREMENTS

 Total cholesterol (TC) = atherogenic (LDL, IDL, VLDL) + anti-atherogenic (HDL)
fractions
 HDL-cholesterol = anti-atherogenic fraction – used for risk assessment
 Triglycerides (TG) = not directly atherogenic, but is a risk modifier – component of the
metabolic syndrome, marker of secondary hyperlipidaemias
o 12h fasting sample <4.5 is required to be able to calculate LDL
 LDL-cholesterol = atherogenic fraction
o Calculated through Friedewald equation LDL = TC – (HDL + TG/2.2)
o Requires fasting to eliminate post-prandial lipoproteins to ensure a constant cholestero
ratio
 Non-HDL cholesterol = total atherogenic lipoproteins – can be used when ↑TG or if patient is n
fasting
o Non-HDL = TC – HDL
 Apolipoproteins can be used to assess risk and as treatment targets
o Apo-A1 – part of HDL
o Apo-B100 – part of LDL, IDL, VLDL
o Apo-B48 – part of chylomicrons, chylomicron remnants
o Lipoprotein(a) – a highly atherogenic form of LDL
 Fasting separates different lipids and excludes chylomicrons and chylomicron remnants from
testing

PRIMARY DYSLIPIDAEMIAS
Familial Hypercholesterolaemia
 ↓ receptor mediated LDL clearance – autosomal co-dominant – mutation in LDLR, APOB, PCSK9
gene
 Affects 1 in 250
 Lipid profile: ↑LDL, TC 9-12, ↓/N fasting TC
  Clinical features: tendon xanthomas, corneal arcus, planar digital and natal cleft
cutaneous xanthomas, aortic stenosis
 Simon Broome diagnostic criteria
o Total cholesterol >7.5 or LDL >4.9
o Tendon xanthomas in patient or 1st/2nd degree relative
o DNA evidence of LDL receptor mutation
o FH of premature MI – <60 in 1st degree relative, <50 in 2nd degree relative
o FH of total cholesterol >7.5
 CHD risk is very high – 50% will be symptomatic by age 50(male) or 60(female)

Familial Combined Hyperlipidaemia (FCH)

 Overproduction of VLDL and Apo-B
 Affects 1 in 100
 Lipid profile: ↑LDL, TC 6.5-10, TG 2.3-6, ↓HDL, non-HDL/ApoB ratio <5, VLDL/total TG ratio
<0.69
 Appears to be autosomal dominant, but more complex
 Clinical features: non-specific, xanthelasma
 CHD risk is less severe, but is linked to HTN, obesity and diabetes

Remnant Type III Hyperlipidaemia (AKA Familial Dysbetalipoproteinaemia)

 ↓ receptor mediated remnant clearance
 Homozygosity for ApoE2 isoform – autosomal recessive, low penetrance
 Affects 1 in 5000
 Lipid profile: TC 8-16, TG 4.5-9, beta VLDL remnants present, non-HDL/ApoB ratio >5,
VLDL/total TG ratio >0.69
 Clinical features: striate palmar and tuberoeruptive xanthomata
 Causes severe early onset atherosclerosis

Familial Hypertriglyceridaemia
 Mild forms are multigenic, severe forms are monogenic (lipoprotein lipase or ApoCII
deficiency)
 Affects 1 in 300
 Lipid profile: TG 2.3-10 in mild-moderate, TG >10 in severe, ApoB normal, small dense LDL
 Clinical features: eruptive xanthomas, lipaemia retinalis
 CHD risk is variable – severe forms are prone to pancreatitis, metabolic syndrome and DM

SECONDARY DYSLIPIDAEMIAS
 Conditions: diabetes, hypothyroidism, renal failure, nephrotic syndrome, cholestasis,
gout, anorexia nervosa, hypopituitarism
o All increase LDL or VLDL and triglycerides
 Lifestyle: alcohol excess, obesity, pregnancy
o All increase LDL or VLDL and triglycerides
 Drugs increasing HDL: anticonvulsants
 Drugs increasing LDL/VLDL and triglycerides: androgens, oestrogens, antipsychotics, β
blockers, corticosteroids, cyclosporine, anti-retrovirals, retinoids
 Drugs decreasing HDL: androgens

Investigations to Exclude Secondary Hyperlipidaemias

 Renal profile excludes renal failure Na⁺, K⁺, creatinine, eGFR
 Liver profile excludes cholestasis and M protein TProt, Alb, ALP, ALT, GGT
 Thyroid profile excludes hypothyroidism TSH, FT4
 Fasting glucose/HbA1c excludes diabetes glucose
 Urinalysis excludes nephrotic syndrome protein