Week 56: Atherosclerosis Flashcards
what is the framingham heart study and what factors risk factors does it cover?
large caucasian cohort study that predicts 10 year risk of angina, MI, death from CHD
age, sex, total cholestrol, HDL, smoking, diabetes, htn and fhx premature cvd
what is the inter-heart study and what are the 9 risk factors?
larger heart study with inc variation of participants
smoking, dm, htn, abdo obesity, psychosocial index, apoB-apoA1 ratio
protective: exercise, fruit/veg, alc
what does apo-B meausre?
LDL and non-HDL cholesterol good predictor of cvd
briefly explain dietary fat digestion
- fats emulsified in small intestine by bile salts from liver, and lipase/ colipase from pancreas (chyme in duodenum is major stim for release of pancreatic lipase and colipase)
- cholesterol esters go to cholesterol and FFA by enzymes
- micelles form and move into intest wall (mono and FFA move by simple diffusion)
- end products form chylomycrons, travel in lymph to body
what does lipoprotein lipase do?
sits on cap overlying adipose, skeletal muscle and other tissues to digest TG and deliver FA to tissues for immediate and stored energy
what is primary and secondary dyslipidemia?
genetic, LDL >4.5, tot chol >6.5, TG>3
unrelated to genetics, minor elevations of lipids
what are the five physical signs of genetic hyperlipidemia?
- tendon xanthomas
- palmer xanthomas
- eruptive xanthomas
- xantholasma
- corneal arcus
what are the five dyslipidemias?
- familial hypercholesteremia (most common, LDL-R does not bind apo-B properly- not a lot of receptor, not breaking down LDL)
- familial combined hyperlipidemia
- disbetalipoproteinemia
- lipoprotein lipase deficiency
- tangier dx (no HDL)
what would your blood work values need to be to start statin therapy?
ldl >2 or
apo-B >0.8 or
non-HDL >2.6
what do statins, PCSK9i, and ezetimibe do?
slow down liver production of cholesterol, inc removal of LDL from blood (to make bile)
block PCSK9 from breaking down LDL-R
blocks absorption of chol in small intestine
what are four things endothelial cells do in arteries?
- tight jxn to protect subendothelial space from blood borne elements
- maintain non thrombotic luminal surface
- maintain smc’s relaxed state (reg of flow sensitive to vasc tone)
- antioxidant properties (superoxide dismutase)
how to smc’s fxn normally?
modulate diam and tone of vessel, normally relaxed, low fxn for making ECM
how does ECM fxn normally in vessel?
structural integrity, strength and flexible components
what parts of vessels are more exposed to non-laminar blood flow more than others and what can occur in these locations when damaged from non-laminar flow?
bends/ branches in vasculature,
activation of pro-atherogenic gene expression cascades by endothel cells (inc stickiness for WBCs), dec NO, inc ET, apoptosis
what can happen if you have loss of endothelial alignment in vessel? (3 things)
- inc luminal adhesion
- changes in subendothelial matrix/ lipid retention
- inc dendritic cells/ uptake oxLDL
bonus: endothelial cells are also less resistant to platelet aggregation, so thrombins can form
What causes WBC to go into subendothelial space (and what is fancy name)
subendothelial chemokines,
diapedesis
what part of the arterial intima retains lipids?
proteoglycans
this promotes inc foam cell production (macrophages engorging lipids)
what happens to smc’s in athero?
inc contractile mediators, dec vasodilation, inc inflamm mediators, inc migration of smcs into subendo space, inc free radicals, excess ecm
how does thrombus form over plaque?
endo cells less resistant to platelet aggregation
disrupted plaque leaks out factors and contents into blood, which triggers clot formation
what is a vulnerable plaque
large lipid core, few smc’s, many foam cells
what are the 6 things to optimally treat/ prevent atherosclerosis
asa (dec platelets)
statin/ ezetimibe/ PCSK9i (dec chol, dec LDL, dec foam cells, inc endo fxn)
smoking cessation (dec oxLDL, dec platelet activation, dec constriction, inc endothel fxn)
anti-hypertensive (dec endo cell barotrauma)
dm therapy (dec glycated products)
exercise (inc blood flow)
briefly describe myocyte phys
depol sarcomere inc ca into sarcoplasm
inc ca, inc ca from SR, (at rest, trop blocks formation of strong attachments between myosin and actin), ca binds trop, releases from actin binding site, allows strong cross bridging to occur, ATP used to flex sarcomeres to shorten
briefly describe myocyte phys
depol sarcomere inc ca into sarcoplasm
inc ca, inc ca from SR, (at rest, trop blocks formation of strong attachments between myosin and actin), ca binds trop, releases from actin binding site, allows strong cross bridging to occur, ATP used to flex heads to shorten sarcomeres, after flexion heads detach
what product to do you get from b oxidation and glycolysis
acetyl co a, goes to krebs to make ATP and O2, need O2 for this process to work
coronary flow to the LV is almost entirely __________ because why?
diastolic bc vessels get compressed w heart contraction
what is the equation for coronary perfusion gradient
CPG= aortic root P - LV pressure (which is why need to maintain reasonable HR so blood can get to coronary vessels during diastole)
what are the four main mechanisms for coronary vascular tone?
- metabolic (ie ischemia inc adenosine, H+, K+, CO2, dec O2), causes vasodilation and relax of pre cap sphincters
- endothelial - NO
- neurogenic - symp vs parasymp
- myogenic- autoreg depending on flow in muscle walls
what are the three major determinants of myocardial demand?
- wall stress (ie wall stress = r x P/ 2w), inc radius (preload), inc pressure inc O2 requirement, inc wall thickness dec O2 requirement
- contractility
- inc heart rate
what causes chest discomfort in angina
adenosine from ischemia
what is the stenosis percentage that would cause reduction in max coronary flow (during exertion)
70-75%
what happens when you have a full occlusion (acute dec in supply)
ruptured plaque and occlusive thrombus at the site of rupture, occlusion longer than 15min causes infarct
what are the embryological origins of:
R/L vent
rough R/L atria
smooth RA
smooth LA
limbus fossa ovalis
floor fossa ovalis
coronary vessel endothelium
coronary vessel media/ adventitia
epicardium
primitive ventricles
primitive atria
sinus venosus
pulmonary veins
septum secondum
septum primum
sinus venosus
epicardium CT
pro-epicardial organ
what are the three criteria for stable chest pain
- substernal chest pain
- provoked by exertion/ emotional stress
- relieved by rest/ nitro
what is unstable angina?
vulnerable plaque, inc freq angina
what is a non-ST elevation MI?
pos biomarkers. plaque rupture/ non-occlusive thrombus
what is a STEMI?
ECG changes, imaging evidence, plaque rupture/ erosion w occlusive thrombus
what are four mechanisms of mortality post PI and how would you treat them?
- mechanical comp (ie MV regug, VSD), beta blocker
- HF (ACEi/ARB, B blocker, MRA, SGTL2i)
- recurrent MI: treat dec lipids, HTN, DM, smoking
- vent arrythmia: b blocker, LVEF preservation, aut implantable defib
how would you treat someone following a percutanous intervention for a STEMI
DAPT one year with ASA and ticagrelor, then reassess bleeding risk, if it is low, DAPT for 3 years with DAPT ASA and ticagrelor or clop, if high bleeding risk, SAPT asa or clop
if elective, DAPT for only 6 months
*can do DAPT for different times based on pt history
when would you consider putting someone on inc treatment after having max statin dosing?
LDL>1.8, apoB ?0.7, nonHDL >2.4, put on ezetimibe and or PCSK9i
what is the pneumonic for critical dx of chest pain, what blood tests/investigations would you order
PET MAC
P: pneumo, PE, panic disorder
E: esophageal rupture, GERD
T: tension pneumo
M: MI
A: aortic disection
C: cardiac tompanade, chest wall pain
CBC, lytes, cr, trop
CXR, ECG, Go right to CTA if suspected PE, AD, MI
what would you think if saw inverse T waves on ECG
ischemia
what leads are affected in a RCA blockage?
II, III, avF (inferior leads)
If you had ST elevation with some PR depression in all leads, what would you think?
pericarditis baby
what is the most common cause myocarditis
virus
what vessel occlusion would cause ant lead ST elevation (V3, V4)
LAD most likely
what are the three diets recommended for CVD prevention
DASH
Med
Portfolio
also replace sat fat w polyunsat fats,
what is the highest rf for atherosclerosis
apoB:apoA1 (hypercholesterolemia)
what is ideal exercise prescription?
150 min mod activity per week or 75 min vig intensity plus 2 days a week resistance training, dec sedentary behav
follow FITT VP
freq
intensity (borg scale, HR: mod 40-60% vs vig: 60-80%)
time
type
volume
progression
