Dyslipidemia and CVD Flashcards
dyslipidemia is a disease. true or false
FALSE, it isn’t a disease but a major risk factor for developing cardiovascular diseases
what has caused the important decrease in mortality from CVD in Canada? (40% decrease)
- improvements in control of CVD risk factors and medical management of patients with CVD
- new clinical data available -> may enhance prevention and management of CVD
what are the roles of the cardiovascular system
- regulate blood flow to tissues
- thermoregulation
- hormone transport
- maintenance of fluid volume
- regulation of pH
- gas exchange
why is it important to regulate blood flow to tissue?
- delivers oxygenated blood and nutrients
- retrieves waste products
what are the major forms of cardiovascular disease?
- hypertension
- atherosclerosis
- coronary heart disease (CHD)
- peripheral vascular disease
- congestive heart failure (CHF)
what are examples of peripheral vascular disease
- cerebrovascular disease (stroke)
- deep vein thrombosis
what is atherosclerosis
the thickening of the blood vessel walls caused by presence of atherosclerotic plaque
what is the effect of atherosclerotic plaque
results in restriction of blood flow due to reduced radius/diameter of blood vessel
what can atherosclerosis be associated with?
- myocardial infarction (MI)
- cerebrovascular accident (CVA; stroke)
- peripheral vascular disease
- CHD
- CHF when severe CHD or MI occurs
what does atherosclerosis involve?
- endothelial cells
- smooth muscle cells
- platelets
- leukocytes
how does atherosclerosis begin?
begins as a response to endothelial lining injury caused by HTN/high BP that results in an inflammatory process
atherosclerosis is _____ until it progresses to ____
asymptomatic until it progresses to ischemic heart disease [lack of blood supply to heart]
explain process of formation of the atherosclerotic plaque
- monocytes (phagocytic white blood cells) circulate in the bloodstream and respond to injury on the artery wall
- monocytes slip under blood vessel cells and engulf LDL cholesterol which also infiltrate the wall either between cells or through diffusion in cell membrane => LDL OXIDATION [atherogenic]
- they become foam cells. The thin layers of foam cells that develop on artery walls are known as fatty streaks and generates inflammation
- a fatty streak thickens and forms plaque as it accumulates additional lipids, smooth muscle cells, connective tissue, and cellular debris
- the artery may expand to accommodate plaque. when this occurs, the plaque that develops often contains a large lipid core with a thin fibrous covering and is vulnerable to rupture and thrombosis
with atherosclerosis there is a moderate elevation of ____. what is it a good indicator of
CRP protein levels - good indicator of inflammation because cytokines, secreted due to inflammation caused by foam cells, generate CRP synthesis in the liver
what is the atherosclerotic plaque made up of
smooth muscle cells, LDL-c, monocytes, mixture of lipids, connective tissue, calcium
what is more dangerous that then restriction of the blood flow caused by atherosclerotic plaque?
the rupture of the plaque -> release of all component sin blood which could block small capillaries/vessels
HTN is a risk factor for rupture
what are the potential primary causes of damage to endothelial wall
- high BP
- chemicals from tobacco
- oxidized LDL
- glycated proteins
- decrease in nitric oxide
- angiotensin 2 [decrease levels of NO which is protective to endothelial wall]
what are the tow hypothesis of atherogenesis?
- endothelial-injury hypothesis
- lipid-infiltration hypothesis
but they are LINKED
why are the 2 hypothesis of atherogenesis linked?
lipid-infiltration causes LDL to be oxidized by macrophages and in turn causes endothelial-injury + fatty streak caused by foam cells from lipid-infiltration also causes endothelial injury
as ratio of LDL:HDL >3:1 increases, there will be high risk for ____
atherosclerosis
what are the risk factors of atherosclerosis
- family history
- age and sex
- obesity
- dyslipidemia
- hypertension
- physical inactivity
- diabetes mellitus/pre-diabetes
- smoking
- obstructive sleep apnea [hypoxia]
there is a genetic factor in development of atherosclerosis. true or false
true, there is predisposing genes
atherosclerosis is more prevalent in ___. why?
in men [like any cardiovascular disease]
because estrogen has a protective effect just like in HTN
why is HTN a big risk factor in developing atherosclerosis
it may initiate atherosclerotic lesion and can also cause plaque to rupture
what are the specific risk factors of dyslipidemia?
- hyperlipidemia (LDL-c)
- low HDL-c (<1.0mmol/L for men and <1.3 for women)
normal HDL levels are the same for men and women. T or F
False: women naturally have more HDL-c
men: >1.0mmol/L
women: >1.3mmol/L
about chylomicrons
- Apo B-48!!! [only found in CM because synthesized by intestine]
- produced and packed in intestine
- high content in TG coming from diet
- biggest of all lipoproteins
- circulates throughout body/tissues/blood vessels
- Apo C-2 stimulates activity of lipoprotein lipase which hydrolyzes TG in CM to FFA taken up by tissues -> decrease size of CM => CM remnant with less TG and more cholesterol esters
- remnants comes back to liver where it is completely disaggregated and cholesterol and TG are repacked in VLDL
circulation of CM
CM goes through lymphatic system [much larger vessles] where it is broken down into CM remnants before they go into the liver
about VLDL
- Apo B-100!!!
- VLDL is synthesized in liver and secreted
contains alot of TG [from both diet from de novo lipogenesis bu liver and from FFA coming from adipose tissue to the liver] but in less amounts than in CM - smaller than CM
metabolism of VLDL
VLDL is secreted from liver as lipoprotein and in the circulation, there are interactions and exchanges between HDL and VLDL where HDL exchanges cholesterol from reverse cholesterol circulation transport and TG from VLDL to HDL
=> mature VLDL particle which circulates into all tissues, app C2 activates LPL and FFA taken up by tissue and stored in adipose tissue
-> remnant either becomes LDL or is taken up by liver
how is VLDL remnant taken up by liver
recognition of LDL receptor with interaction of Apo E and Apo B-100 - endocytosis with receptor
how is VLDL remnant turned into LDL
VLDL remnant is hydrolyzed by hepatic triglyceride lipase -> LDL with less TG content and more cholesterol
characteristic of LDL
has Apo B100
low TG
high CE
characteristics of HDL
- Apo A1!!!
- highly dense
- small
- has alot of Apo protein and phospholipids on its surface
- contain mostly cholesterol from reverse transport
difference between nascent HDL and HDL
nascent HDL has unesterified cholesterol - transformed into cholesterol esters by LCAT -> HDL
transfer and exchanges between HDL and VLDL
HDL transfers cholesterol esters to VLDL
VLDL exchanges TG to HDL
what is the fate of cholesterol
cholesterol is mainly excreted through feces but it also excreted through its conversion in bile acids which is secreted in intestine [recycling/reabsorption of cholesterol]
target for total cholesterol levels in serum
<5.2 mmol/L
target for HDL cholesterol levels in serum
1.0-1.5 mmol/L
>1.0 men
>1.3 women
target for LDL cholesterol levels in serum
<2.6 mmol/L
target for triglyceride levels in serum
<1.7 mmol/L
can you measure LDL-c levels directly?
no - indirect measurement using equation => substation of other measures
comes from Total cholesterol, HDL, and TG levels
when is LDL-c equation not recommended/valied
when TG are higher than 4.5mmol/L
what are the functions of apoproteins
- synthesis/secretion of specific lipoproteins [apo B-100 stimulates synthesis and secretion of VLDL]
- stabilize surface coat of lipoproteins
- activate enzymes (apo C-2 activates LPL)
- interact with cell surface receptors (B-100 and LDL receptors on liver)
apoproteins are the primary determinants of the ____ of lipoproteins
metabolic fate
apoproteins reflect changes in ______ and is indication of ______ in plasma
lipoprotein composition
lipoprotein concentration
which is the better predictor of heart disease: apoprotein levels or lipid levels (LDL)
apoprotein levels - better diagnosis o lipoprotein disorders and risk for developing CHD and CVD because they are indicative of lipoprotein concentration and reflect changes in lipoprotein composition
lipoprotein and they’re associated apoproteins
chylomicrons - B-48
VLDL - B-100
LDL - B-100
HDL - A-1, A-2
which are the most frequent genotypes of Apo-E
E-3/E-3
E-3/E-4
=> associated with better binding of the poE with LDL receptors
how many alleles are associated with apoE
4
E-4/E-4 is associated with ____
dementia
E-2/E-2 genotype is very rare. why is it not a good genotype to have?
Apo E-2/E-2 does not bind to LDL receptors -> increase in VLDL remnants => very high triglyceridemia
what are the two classification of dyslipidemia?
primary and secondary, secondary being the most common one
what is primary dyslipidemia
single or polygenic abnormalities affecting lipoprotein function resulting in hyperlipidemia or hypolipidemia
what is the diagnosis for primary dyslipidemia based on
- history (age at onset, family members)
- physical signs (xanthomas)
- lab analysis: really high lipid profile values, absence or presence of apoproteins, LPL activity
- appearance of serum
- genetic sequencing for rare cases
what are xanthomas
accumulation of small bubbles of connective tissue mixed with cholesterol
what is secondary dylipidemia
from environmental causes +/- predisposition
which are the three types of hypolipoproteinemias associated with primary dyslipidemia
- abetalipoproteinemia
- familial hypobetalipoproteinemia
- familial alpha-lipoprotein deficiency
what is abetalipoproteinemia
- defect in apoprotein B synthesis
- no chill, VLDL, LDL formed and TAG accumulate in liver and intestine
what is familial hypobetalipoproteinemia
- LDL concentration in 10-50% of normal but chylomicron formation occurs
what is familial alpha-lipoprotein deficiency (Tangier disease)
- virtual absence of HDL (Apo-A1), CE accumulates in tissues
- Chylo, VLDL, LDL are all normal
- moderate hyperTG
what are the 2 most common phenotypes of hyperlipoproteinemia?
IIb and IV