Lipids and CVD Flashcards
what are lipids
organic compounds
poorly soluble in water but miscible in organic solvents
what are the important lipids in human physiology
steroids - cholesterol, steroid hormones
fat-soluble vitamins - A, D, E, K
phospholipids
sphingolipids
triglycerides
important lipids in CVD
cholesterol and triglycerides
they are components of lipoproteins, this is how they are transported around the blood stream
cholesterol provides flexibility and strength to the phospholipid bilayer
triglycerides acts as an energy source
what is a lipoprotein
particle that has a phospholipid monolayer rather then bilayer
the hydrophobic tail points towards the cell centre, in the centre there is lots of hydrophobic contents
what are the types of lipoproteins
chylomicrons - high triglyceride, low cholesterol, biggest
very low density lipoprotein - slightly lower triglyceride, slightly higher cholesterol
intermediate density lipoprotein - higher cholesterol, lower triglyceride, very short-lived
low density lipoprotein - higher cholesterol, lower triglyceride, long-lived
high density lipoprotein - highest cholesterol, lowest triglyceride, smallest, long-lived
LDL and HDL play the biggest roles
where are lipoproteins created
small intestine - dietary lipids
liver - endogenous lipids
transport pathways of lipids
stored within hepatocytes or absorbed from gut and secreted into the circulation to deliver cholesterol and/or triglycerides
reverse cholesterol transport - hdl plays a key role, delivers lipids back to the liver
describe exogenous lipid pathways
delivers lipids from the gut to the peripheral tissues
dietary lipids from the small intestine are packaged into chylomicrons
these are secreted into the lymphatic system and then to the circulation
one they are in the circulation they’re broken down by lipoprotein lipase, which breaks down the triglycerides, these become fatty acids which can be taken up and stored in muscle or adipose tissue and used as an energy source
as they are progressively broken down they lose more triglyceride content until they become a micro remnant and return to the liver and stored in the hepatocytes
describe endogenous lipid pathways
originates in the liver
VLDL - triglyceride rich, low cholesterol content
delivers triglyceride to peripheral tissues and is progressively broken down and form IDL, most of these are taken up by the liver
if they are not taken up by the liver they are further broken down by hepatic lipoprotein lipase and become LDL, which is primarily cholesterol rich
what is the main function of LDL
deliver cholesterol to the peripheral tissues
has a protein that latches onto the LDL receptor, this enables LDL to be taken up by cells, and for cholesterol to be delivered to the cells
any remaining LDL is taken up by the liver using the same mechanism
function of HDL
created in the liver and the gut
collects cholesterol from the peripheral tissues
cholesterol can be secreted from cells via the ABC1-A1 transporter, via LCAT (enzyme) which esterifies it and makes it hydrophobic so it can be taken up by hdl
it is then taken up by the liver where it is stored
alternatively VLDL can take cholesterol from HDL via the enzyme CETP, this can disrupt the pathway and has implications for the levels of HDL
what do apolipoproteins do
determine lipoprotein behaviour
lipids and their connection to CVD
elevated HDL decreases rates of CVD
elevated LDL increases rates of CVD
mechanism of atherosclerosis and lipoproteins
if not cleared by the liver LDL can be taken up into arterial walls
LDL accumulation in arterial wall can be maximised by high concentration of LDL and damage to arterial wall (hypertension, oxidation or glycation)
leads to the formation of fatty streaks
how do fatty streaks from
LDLs oxidised by oxygen free radicals and are consumed by macrophages
macrophages laden with LDL are known as foam cells
fatty streak is a collection of foam cells within the arterial wall
how do oxygen free radicals from
glycation reactions (diabetes)
toxins from cigarette smoke
macrophages
atheromatous plaque formation
smooth muscles cells are stimulated by macrophages to migrate, proliferate and differentiates
SMCs differentiate into fibroblasts which produce a fibrous collagen cap
foam cells undergo necrosis or apoptosis to leave a pool of extracellular cholesterol
atheroma is a cholesterol pool beneath a fibrous cap within arterial wall
mechanism of plaque rupture
cholesterol rich lesions (area of abnormal tissue) are more likely to rupture and cause thrombosis (formation of a blood clot) this causes total lumen obstruction and causes tissue ischaemia (leads to MI if in coronary arteries)
fibrous lesions have less cholesterol and are less likely to rupture, this created reduced blood flow (stable angina if in coronary arteries)
what is familial hypercholesterolaemia
inherited disorder of lipoprotein metabolism (form of lipid-driven CV disease)
autosomal dominant
mutation in LDL receptor leads to high LDL levels
if left untreated it can lead to premature CHD onset
be suspicious if there is a family history of hyperlipidaemia or premature CVD, unusually high levels of LDL despite v healthy lifestyle, history of hyper lipidaemia from a young age
what is a stigmata of hyperlipidaemia
cholesterol can deposit in other parts of the body
most commonly found on the surface of tendons (tendon xanthoma), in the cornea of the eye (corneal arcus)
how is cholesterol measured
measure the total cholesterol in the bloodstream
measure the amount of HDL and triglycerides in the bloodstream
LDL is calculated , not measured using the freidewald equation, relies on being able to measure the total cholesterol, the total HDL, and there being a fixed relationship between triglycerides and LDL
specialist labs can measure concentrations of lipoproteins and apolipoproteins
types of prevention of CVD
primary - individuals without disease
secondary - individuals with disease
describe secondary prevention
crucial as there is a >20% risk of any CV event over 10 yrs
lifestyle changes
drugs - ace inhibitor or beta-blocker (reduce post MI mortality), aspirin or clopidogrel (reduce CVD recurrence and mortality), statins (reduce CVD recurrence and mortality)
describe primary prevention
lifestyle change - diet (reduce saturated fats, simple carbs, salt), aerobic exercise, aim for BMI of 20-25, reducing alcohol intake, quit smoking
can offer drugs like statins or blood pressure lowering meds but is controversial as these individuals don’t have a disease yet
who do we treat in primary prevention
based on potential benefit vs side effect - risk of serious side effect must be small, must produce a reasonable reduction in risk
treat those at the highest absolute risk (risk of CV event over 10 yrs), use a risk calculator such as QRISK
if high risk treatment is lifestyle advice and statin
effects of lipid-lowering drugs
statins - reduce LDL, lower risk of CHD, 1st choice for CVD prevention
ezetimibe - reduce LDL, lower risk of CHD, usually an adjunct (supplementary)
fibrates - reduce LDL and triglycerides, increase HDL, only beneficial where low HDL and high trigs, used as an adjunct
mechanism of action of statins
HMG-CoA reductase inhibitors (enzyme that makes cholesterol), inhibit rate limiting step of cholesterol synthesis, intracellular cholesterol depletion which leads to increased LDL uptake
mechanism of action of ezetimibe
inhibits cholesterol absorption at small intestine, binds to Nieman-pick C1 like 1 protein which is a critical mediator of cholesterol absorption in GI epithelial cells
