primary and secondary dyslipidaemias

Question 1

describe the framingham heart study? 9

Answer 1

• 1948
  -investigate epidemic of coronary disease in the USA
  -identify risk factors that contribute to CVD
  major CVC risk factors:
• HBP
  -HBC
  -smoking
  -obesity
  -diabetes
  -physical inactivity

Question 2

describe the cholesterol treatment trialists collaboration? 6

Answer 2

• 1994
• international group involving statisticians and research scientists
• largely focused on stain therapy and their efficacy and safety
• having been collected from 30 major statin trials
• reduction of LDL cholesterol using stain reduced risk of major vascular events and mortality
• affective in a wide range of people

Question 3

describe the copenhagen city heart study? 7

Answer 3

• white men and women
• aim to prevent coronary heart disease and stroke
• describing distribution of known CV risk factors
• describing prevalence and incidence for cardio and cerebrovascular disease
• relating morbidity and mortality for variables collected
• forming background for special studies concerning treatment for various disease entities
• studies genetics

Question 4

what are modifiable CVD risk factors? 7

Answer 4

• Smoking
• Obesity
• Sedentary life
• Diabetes
• High cholesterol or abnormal blood lipids
• Hypertension
• Excess alcohol intake

Question 5

what are unmodifiable CVD risk factors? 4

Answer 5

• > 50
• Men
• Family history
• Pre-existing CVD

Question 6

describe risk calculator tools? 4

Answer 6

• Database derived from health records
• Aim to develop and maintain a high-quality database for use in ethical medical research
• Takes traditional risk factors into account and additional risk factors such as ethnicity, deprivation score, blood pressure treatment
• QRISK3 over 10 indicates that primary prevention with statins will be beneficial

Question 7

describe the NICE lipid modification guideline? 7

Answer 7

• Use clinical judgement to interpret CVD scores
• Do not use lipid cut off values alone to judge the likelihood of familial disorder
• CVD risk may be underestimated in people with underlying medical conditions or treatments
• Measure a full lipid profile before starting on lipid modification therapy
• Exclude possible common secondary causes of dyslipidaemias
• Primary prevention (no previous history) 20mg atorvastatin
• Secondary prevention (previous history of CVD) 80mg atorvastatin

Question 8

why do we treat lipid disorders? 2

Answer 8

• To reduces the atherosclerotic process and the incidence of clinical vascular disease
• To prevent pancreatitis which is associated with increased serum triglyceride

Question 9

what are low density lipoprotein receptors? 3

Answer 9

• Cell surface receptor which recognises ApoB-100 which is embedded in the phospholipid outer layer of LDL particles
• Present on most cells but in the majority on the liver
• LDLR on hepatocytes binds to LDL particles and remove them from the circulation. The LDLR then return to the cell surface to repeat this process

Question 10

what is the first line treatment for hypercholesterolaemia?

Answer 10

statins

Question 11

what is ezetimibe? 2

Answer 11

• Potent and selective inhibitor of absorption of cholesterol in the small bowl
• Impair the intestinal reabsorption of dietary and hepatically excreted biliary cholesterol through inhibition of a membrane transporter

Question 12

describe 2 injectable forms of cholesterol treatment?

Answer 12

• PCSK9 functions as a binding protein, expressed in hepatocytes and after secretion binds to the LDLR and promotes their degradation
• Blocking this allows LDLR to remove LDLC from the circulation

Question 13

how do we identify the pattern of lipoprotein abnormality? 3

Answer 13

• Hypercholesterolaemia= raised TC and LDLC
• Mixed hyperlipidaemia= raised Tc and LDLC with raised TG and low HDLC, seen in patients with a glucose intolerance
• Hypertriglyceridemia= less common, may be familial, cause harm through acute pancreatitis

Question 14

what is lipoprotein(a)? 6

Answer 14

• Macromolecular complex in plasma
• Lipoprotein made by the liver
• LDL-like + ApoB+ Apo (a)
• Association between elevated Lp(a) concentrations and MI, stroke and aortic valve stenosis
• Apo(a): Glycoprotein
• Pathological function: atherosclerosis and thrombosis formation

Question 15

how do we treat dyslipidaemias? 5

Answer 15

• Lifestyle changes
• Approved and investigational drugs
• Lipid apheresis
• PCSK9i
• Antisense therapies

Question 16

what is familial hypercholesterolaemia? 3

how do we treat it? 6

Answer 16

• Common genetic disorder
• Mutations in LDLR gene
• Wide range of age at first cardiovascular event
• Low saturated fat diet and exercise
• Statins
• Cholesterol absorption inhibitor
• Surgery
• Anti-PCSK9
• Involve patient self-help group and DNA testing