Hyperlipidaemia Flashcards
Framingham - major CVD risk factors
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.
Framingham shortcomings
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.
QResearch
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.
QRisk
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.
JBS3 Risk Calculator
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
Modifiable vs Un-mobiliable
Modifiable: Smoking, obesity, sedentary lifestyle, diabetes , hypertension, excess alcohol intake and high cholesterol/abnormal blood lipids
Un-modifiable: Age, gender and family history
National Institute for Health and Care Excellence
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.
Primary prevention
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
Secondary Prevention
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
Fasting Lipid Report - healthy
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)
Why treat lipid disorder
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).
LDL receptor
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.
Ezetimibe
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
Bile Acid Sequestrants (Resins)
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
Fibrates
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).
Omega 3 (Fish oils)
Inhibit lipogenesis and stimulate β-oxidation
Reduced rate of secretion of very low density lipoprotein (VLDL) triglyceride (TG)
Clinical outcome data very limited
PCSK9 inhibitors
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.
Hypercholesterolaemia
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).
Mixed hyperlipidaemia (dyslipidaemia)
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.
Hypertriglyceridaemia
Pure hypertriglyceridaemia is less common
May be familial and (unlike most other dyslipidaemias), tending to cause harm through acute pancreatitis.
Example Fasting Lipid Report in a patient with Heterozygous FH
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)
Treatment of FH
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.
