Hyperlipidaemia

Question 1

Framingham - major CVD risk factors

Answer 1

High blood pressure
High blood cholesterol
Smoking
Obesity
Diabetes
Physical inactivity 

The effects of related factors such as blood triglyceride and HDL cholesterol levels, age, gender, and psychosocial issues.

Question 2

Framingham shortcomings

Answer 2

Based on North American data and, as a result, it is claimed that it overestimates cardiovascular risk in European populations.

It is also claimed that Framingham may underestimate cardiovascular risk in people with diabetes, South Asian men and those who are socially deprived.

Question 3

QResearch

Answer 3

A large consolidated database derived from the health records of over 24million patients from approximately 1300 general practices In the UK and include data from patients who are currently registered with the practices as well as historical patients who may have died or left. Historical records extend back to the early 1990’s.

Aim: to develop and maintain a high quality database of general practice derived data linked to secondary care data for use in ethical medical research.

Question 4

QRisk

Answer 4

QRISK takes into account many of the traditional risk factors included in the Framingham algorithm (eg, age, sex, cholesterol-high density lipoprotein ratio, blood pressure, diabetes and smoking status).

However, it is based on UK data and includes additional risk factors, such as ethnicity, deprivation (measured using the Townsend deprivation score, which is obtained from data associated with a person’s postcode), blood pressure treatment and body mass index.

A QRISK2 over 10 (10% risk of CVD event over the next ten years) indicates that primary prevention with lipid lowering therapy (such as statins) should be considered.

Question 5

JBS3 Risk Calculator

Answer 5

QRISK® Lifetime has been chosen as the basis for the JBS3 risk calculator as it provides the option of a calculation of lifetime risk and is based on a UK population.

-Heart age-Compared to a person of the same age, gender, ethnicity with optimal risk factor
Healthy years- Expected life without a heart attack or stroke

Question 6

Modifiable vs Un-mobiliable

Answer 6

Modifiable: Smoking, obesity, sedentary lifestyle, diabetes , hypertension, excess alcohol intake and high cholesterol/abnormal blood lipids

Un-modifiable: Age, gender and family history

Question 7

National Institute for Health and Care Excellence

Answer 7

Provides national guidance advice, quality standards and information services for health, public health and social care. Also containsresources to help maximise use of evidence and guidance.

Question 8

Primary prevention

Answer 8

No previous history of angina pectoris or a history of documented MI

History of CA procedures (bypass graft or angioplasty), peripheral artery disease, aortic aneurysm, and symptomatic coronary artery disease)

Statin - Atorvastatin 20mg

Question 9

Secondary Prevention

Answer 9

With previous history of angina pectoris or a history of documented MI

History of coronary artery procedures (bypass graft or angioplasty), peripheral artery disease, aortic aneurysm, and symptomatic coronary artery disease)

Statin - Atorvastatin 80mg

Question 10

Fasting Lipid Report - healthy

Answer 10

Total Cholesterol(TC) 4.2 mmol/L (<5, ideal<4)
Triglyceride(TG) 1.2 mmol/L (<1.7)
HDL-Cholesterol (HDL-C) 1.5 mmol/L (>1)
LDL Cholesterol(LDL-C) 2.1 mmol/L (<3, ideal<2)
Non-HDL Cholesterol 2.7 mmol/L (<2.8 or <2.5 on statins)

Question 11

Why treat lipid disorder

Answer 11

Often asymptomatic

To reduce the atherosclerotic process and the incidence of clinical vascular disease.

To prevent pancreatitis which is associated with grossly increased serum triglyceride (>10mmol/L, usually >20mmol/L).

Question 12

LDL receptor

Answer 12

Cell-surface receptor (encoded by LDLR gene) that recognizes ApoB-100 (apolipoproteinB-100) which is embedded in the phospholipid outer layer of LDL particles.

Present on most cells but 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 13

Ezetimibe

Answer 13

Potent and selective inhibitor of absorption of cholesterol in the small bowel.

It reduces the contribution of dietary and biliary cholesterol and therefore reduces the flux of cholesteryl esters into Very Low Density Lipoprotein (VLDL) particles.

Ezetimibe at 10 mg/day has been shown to induce an about 20% reduction in LDLC and 8% reduction in TG

Question 14

Bile Acid Sequestrants (Resins)

Answer 14

Bind bile acids in the intestine, interrupting the enterohepatic circulation of bile.
Increased conversion of cholesterol into bile acids in liver
Increased LDLR activity decreases LDLC but can increase triglyceride as cholesterol synthesis increases
Care with concomitant medication
Treatment limited by constipation and flatulence
Older resins cause oesophageal irritation

Question 15

Fibrates

Answer 15

Binds nuclear PPAR (peroxisome proliferator-activated receptor)
Increase peripheral lipolysis (by activating lipoprotein lipase) and decrease hepatic triglyceride production.

The prominent effect of the fibrates is to reduce triglyceride by 25–50% and secondarily to raise HDL-C by 15–25%.

Clinical outcome data limited (markedly hypertriglyceridaemic post-hoc subgroup analysis is suggestive of benefit).

Question 16

Omega 3 (Fish oils)

Answer 16

Inhibit lipogenesis and stimulate β-oxidation

Reduced rate of secretion of very low density lipoprotein (VLDL) triglyceride (TG)

Clinical outcome data very limited

Question 17

PCSK9 inhibitors

Answer 17

PCSK9 functions as a binding protein; it is expressed primarily in hepatocytes and after secretion binds to the LDLR and promotes their degradation. By blocking PCSK9, these drugs result in increased availability of LDLR to remove LDLC from the circulation.

New class of lipid-lowering medications
Administered bimonthly subcutaneous injections
Monoclonal antibodies to PCSK9
Developed after the observation that naturally occurring loss-of-function polymorphisms resulting in PCSK9 underexpression led to lower LDLC levels.

Question 18

Hypercholesterolaemia

Answer 18

raised TC and LDLC

Such a pattern is typically seen in familial hypercholesterolaemia (FH) where total cholesterol levels may range between 7 and 20 mmol/L (average 9 mmol/L) in heterozygotes but are even higher in the rare homozygotes (15–30 mmol/L).

Question 19

Mixed hyperlipidaemia (dyslipidaemia)

Answer 19

raised TC and LDLC with raised TG, often low HDLC

This pattern is often seen in patients with glucose intolerance and diabetes and arises from the increased production and reduced breakdown of triglyceride-rich lipoproteins.

Question 20

Hypertriglyceridaemia

Answer 20

Pure hypertriglyceridaemia is less common

May be familial and (unlike most other dyslipidaemias), tending to cause harm through acute pancreatitis.

Question 21

Example Fasting Lipid Report in a patient with Heterozygous FH

Answer 21

Cholesterol 11.3 mmol/L (<5, ideal<4)
Triglyceride 1.3 mmol/L (<1.7)
HDL Cholesterol 1.1 mmol/L (>1)
LDL Cholesterol 9.6 mmol/L (<3, ideal<2)
Non-HDL Cholesterol 10.2 mmol/L (<2.8, <2.5 on statins)

(Creatinine, thyroid, liver, glucose, albumin all normal)

Question 22

Treatment of FH

Answer 22

Low Saturated Fat Diet and exercise
Statins
Possible addition of cholesterol absorption inhibitor (ezetimibe)
Rarely resins/surgery/LDL apheresis
Anti–PCSK9
Involve patient self help group, offer DNA testing and get the family tested.