Hyperlipidaemia

Question 1

Definition?

Answer 1

Elevated blood lipid levels-including LDL, total cholesterol and triglycerides.

Question 2

RF?

Answer 2

• FH
• Corneal arcus
• <50 yrs
• Xanthelasmata
• CVD
• FH of CVD<60 yrs
• HT
• DM
• Smoker
• High BMI

Question 3

Epidemiology?

Answer 3

Age:
Sex:
Ethnicity: South Asian

Question 4

Aetiology?

Answer 4

• Common primary-high LDL only
• Hyperalphalipoproteinaemia: ↑hdl, chol >2.
• Hypoalphalipoproteinaemia (Tangier disease): ↓hdl, chol <0.92.
• Abetalipoproteinaemia (abl): trig <0.3, chol <1.3, missingldl,vldland chylomicrons. Autosomal recessive disorder of fat malabsorption causing vitamina&edeficiency, with retinitis pigmentosa, sensory neuropathy, ataxia, pes cavus and acanthocytosis.
• Hypobetalipoproteinaemia: chol <1.5,ldl↓,hdl↓. Autosomal codominant disorder of apolipoproteinbmetabolism. ↑ longevity in heterozygotes. Homozygotes present with a similar clinical picture toabl.
Familial primary-chylomicron, cholesterol, lipid, apolipoprotein, triglyceride
• Secondary hyperlipidaemia-Cushing’s hypothyroidism, nephrotic syndrome, cholestasis
• Mixed-both elevated LDL and triglycerides-T2DM, metabolic syndrome, alcohol abuse, chronic renal failure

Question 5

CP?

Answer 5

• Typically no specific signs or symptoms
• Skinmanifestations
• Xanthoma: nodular lipid deposits in theskinand tendons
○ Pathophysiology: Extremely high levels oftriglyceridesand/orLDLresult inextravasation of plasmalipoproteinsand their deposition in tissue.
○ Eruptive xanthomas: yellowpapuleswith anerythematousborder;located on the buttocks, back, and the extensor surfaces of the extremities
§ Occurrence:hypertriglyceridemia(chylomicronorVLDL); alsolipoprotein lipasedeficiency
○ Tendinous xanthomas: firm nodules, located in tendons(typically extensor tendons of hands and theAchilles tendon)
§ Occurrence: severe hypercholesterinemia, ↑LDLlevels
○ Palmarxanthomas: yellowplaqueson the palms of the hands
§ Occurrence:type III hyperlipoproteinemia,↑VLDL
• Xanthelasmas: nodular lipid deposits around the eyelids
○ Typically bilateral, yellow, flatplaqueson the upper eyelids (nasal side)
○ Etiology:idiopathic; often occurs in association withhypercholesterolemia(e.g.,primary biliary cholangitis), hyperapobetalipoproteinemia,↑LDLlevels
• Increasedincidencein
○ Patients suffering fromdiabetes mellitus
○ Patients withincreased lipoproteins in plasma
○ Usually affectspostmenopausalwomen
• Eyemanifestations
• Lipemia retinalis: opaque, white appearance of the retinal vessels, visible onfundoscopic exam
• Arcus lipoides corneae
• Fatty liver(hepatic steatosis)
• Severehypertriglyceridemia(typically> 1000 mg/dL) →pancreatitis
• Atherosclerosiswith secondary diseases
• Coronary heart disease
• Myocardial infarction
• Stroke
• Peripheral arterial disease
• Carotid artery stenosis
• Cholesterol embolization syndrome

Question 6

Pathophysiology?

Answer 6

See ON

Question 7

Investigations?

Answer 7

• LDL
• HDL
• Cholesterol
• Triglycerides
• Chylomicrons
• Fasting lipid profile
• OGTT
• BP

Question 8

M first line?

Answer 8

• Lifestyle advice.
  
  • Aim forbmiof 20–25.
  • Diet with <10% of calories from saturated fats; ↑fibre, fresh fruit and vegetables, omega-3 fatty acids.
  • ↑Exercise. And weight loss
  • Smoking cessation
  • Hypertension management-see topic

Question 9

M first line pharm?

Answer 9

• Identify familial or 2° hyperlipidaemias. Treatment may differ—see above.
• statins, egsimvastatin(40mgpoat night),
• ↓cholesterol synthesis in the liver.
• ci: porphyria, cholestasis, pregnancy.
• Treatment priorities:using statins in primary prevention may cause side-effects and is expensive.
• Top priority:Treat those with knowncvd(there is no need to calculate their risk: ipso facto they already have high risk).
• 2ndpriority:Treat all those withdm and CKD(especially if risk of cardiac event >2%/yr).
○ atorvastatin 20 mg should be offered if type 1 diabetics who are:
○ → older than 40 years, or
○ → have had diabetes for more than 10 years or
○ → have established nephropathy or
○ → have other CVD risk factors

• 3rdpriority:Those with a 10-year risk ofcvd>20%,irrespective of baseline lipid levels. Current guidelines suggest a target plasma cholesterol of ≤4mmol/L.28There are not yet enough data to support a 4thpriority of giving statins to all men over 50 and women over 65.

Question 10

M second line ?

Answer 10

• fibrates, egbezafibrate(useful in mixed hyperlipidaemias),
• or cholesterol absorption inhibitors, egezetimibe(although unclear if it reduces mortality);
• anion exchange resins, eg colestyramine;
• consider nicotinic acid (hdl↑;ldl↓;
• Hypertriglyceridaemia responds best to fibrates, nicotinic acid, or fish oil.

Question 11

P and C?

Answer 11

• se: myalgia ± myositis (stop if ↑ck≥10-fold; if any myalgia, checkck; risk is 1 per 100,000 treatment-years),27abdominal pain, and ↑lfts (stop ifast≳100u/L). Cytochrome p450 inhibitors ([link]) ↑serum concentrations (eg 200mL of grapefruit juice may ↑simvastatin concentration by 300%, and atorvastatin ↑80%, but pravastatin is almost unchanged).
se: severe flushes; aspirin 300mg ½h pre-dose helps this).
CVD