Cholesterol/CVD

• Total cholesterol consists of LDL-C, VLDL-C and HDL-C
• Total cholesterol rage: less or equal to 5 mmol/L
• Total cholesterol to HDL cholesterol ratio range is <6 mmol/L (less than 4 in high risk individuals)
• Familial hypercholesterolaemia is an inherited condition caused by a genetic mutation in the LDLR, Apo B or PCSK9 gene
• Clinical signs of FH:

  Tendon xanthoma- lipid deposits on knuckles, knees or Achilles

  Xanthalasmas- pale yellow lumps around eye and eyelid

  Corneal arcus- pale white ring around iris
• Treatment for FH is high intensity statins. Atorvastatin 20-80mg or Rosuvastatin 10-40mg. Ezetimibe can be used in conjunction.
• The Simon Broome or Dutch Lipid Clinic Network criteria is used for the diagnosis of HF
• High density lipoprotein (HDL) absorbs cholesterol in the blood and transports it back to the liver
• Low density lipoprotein (LDL) transports cholesterol to cells and deposits. Associated with increased risk of CVD.
• Cholesterol is synthesized in the hepatic cells of the liver
• Cardiovascular disease (CVD) risk factors include: previous CVD, smoking, diabetes, hypertension, hyperlipidaemia, chronic inflammatory disorders, family history of early onset CVD and cocaine use
• QRISK3 calculates your risk of a heart attack in the next 10 years by using factors such as age, ethnicity, smoking status, cholesterol and BMI
• Low risk QRISK3 = <10%

  High risk QRISK3= >20%

  Patients with a QRISK 3 >10% should commence lifestyle changes but if ineffective/ inappropriate they should be offered statin treatment
• Primary prevention of CVD= 20mg OD atorvastatin

  Primary prevention is to prevent the atherosclerotic process
• Secondary prevention of CVD= 80mg atorvastatin

  Secondary prevention is the treatment of an already there atherosclerotic process
• Atherosclerosis affects the medium and large arteries. It is caused by chronic inflammation and activation of the immune system in the artery wall. This causes the deposition of lipids in the artery wall, followed by the development of fibrous atheromatous plaques.

  These plaques result in:

  • Stiffening
  • Stenosis
  • Plaque rupture
• Stiffening of the artery walls leads to hypertension (raised blood pressure) and strain on the heart as it tries to pump blood against extra resistance.

  Stenosis leads to reduced blood flow (e.g. in angina).

  Plaque rupture creates a thrombus that can block a distal vessel and cause ischaemia. An example is acute coronary syndrome, where a coronary artery becomes blocked.
• Non-modifiable risk factors:

  • Older age
  • Family history
  • Male
• Modifiable risk factors:

  • Raised cholesterol
  • Smoking
  • Alcohol consumption
  • Poor diet
  • Lack of exercise
  • Obesity
  • Poor sleep
  • Stress
• Medical co-morbidities increase the risk of atherosclerosis and should be carefully managed to minimise the risk:

  • Diabetes
  • Hypertension
  • Chronic kidney disease (CKD)
  • Inflammatory conditions, such as rheumatoid arthritis
  • Atypical antipsychotic medications
• End Results of Atherosclerosis

  • Angina
  • Myocardial infarction
  • Transient ischaemic attacks
  • Strokes
  • Peripheral arterial disease
  • Chronic mesenteric ischaemia
• Atorvastatin 20mg is offered as primary prevention to all patients with:

  • Chronic kidney disease (eGFR less than 60 ml/min/1.73 m2)
  • Type 1 diabetes for more than 10 years or are over 40 years
• Statins reduce cholesterol production in the liver by inhibiting HMG CoA reductase.
• Rare and significant side effects of statins include:

  • Myopathy (causing muscle weakness and pain)
  • Rhabdomyolysis (muscle damage – check the creatine kinase in patients with muscle pain)
  • Type 2 diabetes - impair body's ability to use insulin effectively
  • Haemorrhagic strokes (very rarely)
• Several common medications interact with statins. One key interaction to remember is with macrolide antibiotics. Patients being prescribed clarithromycin or erythromycin should be advised to stop taking their statin whilst taking these antibiotics.
• Other cholesterol lowering drugs:

  • Ezetimibe - inhibits absorption of cholesterol in the intestine
  • PCSK9 inhibitors (evolocumab and alirocumab) - monoclonal antibodies - given as a SC injection