hypercholesterolemia Flashcards
cholesterol
steroid released by the liver and intestines
cholesterol function
regulates cell membrane fluidity and helps produce vitamin D, steroids and bile
triglyceride pathway
triglycerides get transported by VLDL from the liver or chylomicrons from the intestines to adipose tissue for energy and storage
cholesterol pathway
cholesterol gets transported by LDL for plasma membranes and steroid synthesis or HDL for excess to be converted into bile
atherosclerosis
lipid deposition and plaque reaches critical point where disruption occurs and overlying thrombus forms which obstructs blood flow
hypercholesterolemia causes (8)
diabetes, hyperthyroidism, pregnancy, menopause, CKD, liver disease, gout, FH
normal total cholesterol
<5 mmol/L or <200 mg/dl
normal HDL
> 1 mmol/l or 40-60 mg/dl
normal LDL
<3 mmol/l or <100 mg/dl
normal non-HDL
<4 mmol/l
normal triglycerides
<2.3 mmol/l
familial hypercholesterolemia
autosomal dominant disorder involving high LDL-C
heterozygous familial hypercholesterolemia
inherited mutation from one parent
homozygous familial hypercholestrolemia
inherited mutation from both parents
hypercholesterolemia diagnosis
total cholesterol >7.5 mmol, check personal or family history of premature CHD, check SBC or DLCN criteria and refer to DNA testing
hypercholesterolemia monitoring
full lipid profile, liver function tests, renal function, HbA1C, TFTs, creatine kinase
full lipid profile
aim for >40% reduction in non-HDL-C
liver function test
do not start statins if transaminases >3x upper limit, repeat at 3 months and 12 months
renal function test
low statin dose if severe impairment
haemoglobin A1C test
can diagnose diabetes
thyroid function test
can diagnose hypothyroidism
creatine kinase
low statin dose if raised <5x upper limit and persistent muscle pain prior to starting; stop statin if >5x upper limit or experiencing pain
statins function
reduce cholesterol synthesis in the liver by inhibiting HMG-CoA reductase
high-intensity regimen
statin dose that reduces LDL-C by >50%
primary prevention drug
atorvastatin (20mg) daily
primary prevention aim
reduce non-HDL-C by >40%
secondary prevention drug
atorvastatin (80mg) daily, provided after a CV event
secondary prevention aim
reduce LDL-C to <2mmol/l or non-HDL-C to <2.6 mmol/l
atorvastatin contraindications
active liver disease, pregnancy, breastfeeding, antiviral drug interactions
atorvastatin side effects
nausea, indigestion, headaches, nosebleeds, sore throat, cold-like symptoms, constipation, flatulence, diarrhoea
ezetimibe
inhibits cholesterol absorption at brush border of intestine causing increased LDL receptor expression on hepatocyte cell surface and more cholesterol removal
when to offer ezetimibe
primary hypercholestreolemia with side effects to statins
ezetimibe contraindications (3)
increased risk of gallstones, myopathy and rhabdomyolysis, moderate to severe liver impairment
ezetimibe side effects
hypertension, abdominal pain, diarrhoea, flatulence, increased ALT/AST, headaches, fatigue
bempedoic acid
inhibits cholesterol synthesis (combined with ezetimibe)
when to offer bempedoic acid
patients intolerant to statins or contraindicated and LDL-C levels unaffected by ezetimibe
bempedoic acid contraindications
gout, liver conditions, pregnant or breastfeeding
bempedoic acid side effects
anaemia, myopathy with statins, deranged LFTs, reduced eGFR, gout, extremity pain
when to offer icosapent ethyl
triglycerides >1.7 mmol/l and LDL-C 1.04-2.6 mmol/l and established CVD and already on statin
icosapent ethyl contraindications
allergic to fish, hepatic impairment, atrial fibrillation, bleeding risk
icosapent ethyl side effects
atrial fibrillation, bleeding, peripheral oedema, gout, musculoskeletal pain, constipation
inclisiran
increases LDL receptor recycling and expression on hepatocyte cell surface and more cholesterol removal
when to offer inclisiran
LDL 2.6 mmol/l and established CVD and already on maximal tolerated oral lipid lowering therapy
inclisiran warnings
high cost drug approval for hospital use and some GPs reluctant to prescribe
PCSK9 inhibitors
bind PCSK9 to prevent LDL receptor degradation on hepatocyte cell surface and more cholesterol removal
PCSK9 inhibitor examples
evolocumab, alirocumab
PCSK9 inhibitor warnings
expensive
