dyslipidemia and CAD Flashcards
role of TG
- metabolic fuel
role of phospholipids
- metabolic fuel
- lipoproteins
- blood clotting
- myelin sheath
- cell membranes
role of cholesterol
- plasma membranes
- bile salts
- steroid hormones
- other specialized molecules
lipoproteins
- fat carrying proteins that encapsulate and transport cholesterol and TG through blood
apoprotein
- any protein that binds with lipid to form a lipoprotein
- precursor to LDL and HDL
chylomicrons
- carry exogenous TG and cholesterol
VLDL
- carry endogenous TG (mainly) and cholesterol
LDL
- “bad cholesterol”
- carries cholesterol to cells
HDL
- “good cholesterol”
- carries cholesterol from cells
main source of exogenous cholesterol
- diet
- mainly animal sources
main source of endogenous cholesterol
- produced from liver and cells lining the GIT
liver and cholesterol metabolism
- adjusted via pos and neg feedback loops
- results in relatively stable plasma cholesterol lev
- *very difficult to change serum levels with diet alone
what are the ways in which LDL is removed from circulation
- receptor dependent
- non-receptor dependent macrophages
receptor dependent LDL removal
- binds to cell surface receptors -> endocytosis
- LDL degraded -> cholesterol released into cytoplasm and excreted
non-receptor dependent LDL removal
- ingestion of phagocytic monocytes
- macrophage uptake of LDL in arterial wall -> accumulation of insoluble cholesterol ester -> foam cells -> atherosclerosis
dyslipidemia values
- LDL > 160
- HDL < 40
- TG > 150
- all three are independent risk factors for CAD
- ratio of LDL to HDL is important risk factor
what level of HDL is protective
- HDL > 60
how do we measure LDL
- indirectly via friedwald equation
- LDL = total cholesterol - HDL- TG
primary dyslipidemia
- intrinsic causes- familial autosomal dominant mutations
- over production or impaired removal
- strongly linked to premature CAD
- > 200 LDL receptor mutations
- xanthomas, high LDL, FHx
secondary causes of dyslipidemia
- generally modifiable risk factors
- DM2
- obesity
- drugs
- cigarettes
- excessive alcohol
- cholestatic liver disease
- nephrotic syndrome or chronic renal failure
- hypothyroidism
who should be screened for dyslipidemia
- men > 35, women > 45
- men > 25 or women > 35 with CV risk factors
- pts with diabetes
- pts with first degree relative with premature CAD
how often do you screen for dyslipidemia
- every 5 years if clearly above threshold
- every 3 years if near threshold
what is considered premature CAD
- before 55 in men
- before 65 in women
lifestyle modifications to treat dyslipidemia
- diet high in vegetables, whole grains, low or nonfat dairy
- some alcohol
- low red or processed meats
- low sugar intake
what is the standard of care for lipid lowering agents and why
- HMG CoA reductase inhibitors
- AKA statins
- most powerful at lowering LDL, modest HDL increase
- only lipid lowering agent shown to improve CV outcomes both short and long term
- improves all cause mortality
how do statins work
- inhibit HMG CoA reductase which is required for biosynthesis of cholesterol
what should you order before starting statin therapy
- fasting lipid panel
- LFTs
- CK
benefit groups for statins
- clinical atherosclerosis CVD
- LDL > 190, age > 21
- primary prevention for diabetics: age 40-75, LDL 70-189
- primary prevention for nondiabetics: > 7.5% 10 year ACSVD risk, age 40-75, LDL 70-189
monitoring response to therapy with statins
- have pt repeat labs in 4-6 weeks
- high intensity tx should see 50% drop in LDL, mod intensity 30-50%
- if dont get expected drop then have them return in 1 mo and recheck
- if levels still not as anticipated add another agent
what is the best combo agent to use with statins
- ezetimibe
ADRs of statins
- myopathies
- LFT abnormalities- 3X ULN, not common and reversible
myopathies and statins
- myalgia- normal CK
- myositis- somewhat elevated CK > 10X ULN
- rhabdo- markedly increased CK, pain, very ill
- if pt has severe muscle sx or fatigue address possibility of rhabdo via CK, creatinine, UA for myoglobinuria
treatment for mild-mod muscle sx while on statin
- d/c statin until sx are evaluated
- can decrease dose or switch agent
- eval pt for other conditions that might increase risk for muscle sx
- if after 2 mo without statin rx and still have sx or elevated CK it is likely not due to stain
other causes for elevated CK other than statins
- hypothyroid disease
- inflammatory myopathies
- PMR in pts > 50
- injury or excessive exercise
- alcohol misuse
increased risk for statin intolerance
- erythromycin
- cyclosporin
- HIV tx
- grapefruit juice
- combo lipid tx- fibrates and niacin
cholesterol absorption inhibitors
- agent- ezetimibe
- used in combo with statins to further lower LDL
- good alt to high dose statin if pt is intolerant
- monitor liver function
mild-mod hyperTG
- 150-1000 mg/dL
- unclear if tx makes difference for CV outcomes
severe hyperTG
- levels over 1000 mg/dL
- risk of pancreatitis
- lipemic blood samples
tx for hyperTG
- focus on metabolic syndrome
- weight loss*
- aerobic exs- mod intensity for 4 hours a week
- avoid sugars
- strict glycemic control in diabetics
- unclear if any meds make a dif- fish oil, niacin, fibrates
metabolic syndromes
- increased risk of atherogenesis, pro-inflammatory state
- need 3 of 5 risk factors
- glucose intolerance
- HTN
- dyslipidemia ( TG and HDL sep risk factors)
- central obesity- male waist circumference > 40 in., female > 35 in.
what is the leading cause of death in adults in US
- CAD
pathophys of CAD
- atherosclerosis- thickening of arterial vessel wall
- increased vasc resistance -> progression -> complete occlusion d/t ruptured clot -> MI
primary prevention of CAD
- maintain/ achieve ideal weight
- PE and healthy diet
- no smoking
- maintain BP goals at < 140/90 or 130/80 if other known risk factors
- glycemic control in diabetes
- high risk pts should take ASA daily
- small amounts of alcohol consumption
angina pectoris
- chest pain d/t myocardial ischemia
- tightness, squeezing, burning, gas, indigestion or ill characterized
anginal equivalent
- sx other than chest discomfort attributable to myocardial ischemia
- i.e. SOB, dizziness, nausea, fatigue
four main risk factors that affect 02 demand
- HR
- SBP
- myocardial wall tension or stress
- myocardial contractility
how is myocardial ischemia on EKG represented
- ST depressions
stable angina
- asymptomatic at rest
- sx provoked by predictable amount of exertion
unstable angina
- sx at rest or sx with less and less exertion
sx of chronic stable angina
- chest pain or DOE lasting 5-15 min
- predictable and reproducible
- d/t flow limiting lesions
- relieved by rest or NTG
- localized to central or slightly left side of chest
- presyncope and fatigue
physical exam for CAD
- most often normal
- general appearance- central obesity, sweaty, SOB with minimal exertion
- vitals- HTN
- diminished peripheral pulses- PAD
- bruits of carotid, renal, aorta, and femoral aa.
EKG findings in CAD
- often normal in early or stable CAD
- pathologic Q waves- prev MI
- nonspecific St or T wave abnormalities
- LVH- d/t long standing HTN
- ST elevation during STEMI
stress testing
- best method for dx CAD in conjunction with rest of clinical assessment
- appropriate for stable angina
- c/i in unstable angina
what is the gold std for CAD dx
- coronary angiography
- not used often as primary method
- expensive and invasive
- does not have physiologic info
estimating pre stress test probability of CAD
- classic/ typical angina
- probable or atypical angina
- non-anginal or non-ischemic chest pain
- intermediate pretest probability yield most results on stress test
classic/ typical angina
- substernal chest pain
- typical in quality and duration
- provoked by exertion/ stress and relieved be rest or NTG
probable or atypical angina
- chest pain with 2/3 characteristics of classic
non-anginal or non- ischemic ches tpain
- chest pain with one or non of characteristics of classic
indications for stress test
- intermed pretest probability
- pre-op risk assessment for non-cardiac sx
- pts with significant change in cardiac sx
- after resolution of acute chest pain
- prior to angiography to localize lesion
exercise tolerance testing (ETT)
- first line for most pts
- resting EKG cannot have abnormalities
- must be able to exs
- low-mod risk CAD
- women tend to have more false positives
findings on resting EKG that disqualify a pt from ETT
- ST abnormalities
- LVH
- LBBB
- ventricular paced
- WPW
stress echo
- either exs or pharmacologically induced
- echo at rest then after stress
- look for stress induced regional wall motion abnormalities to localize lesions
- operator dependent
radionuclide myocardial perfusion imaging
- either exs or pharmacologically induced
- imaging before and after stress
- inject radioactive nucleotide
- poorly perfused areas of heart do not take up color- localizes lesions
- highly sensitive
- aka stress myoview or stress MIBI
nuclear medicine PET CT stress test
- very sensitive
- very expensive
- best for obese pts
- not readily avail
acute coronary syndrome (ACS)
- unstable angina
- NSTEMI
- STEMI
sx of ACS
- severe chest pressure usually in early morning
- radiates to L arm, both arms, or jaw
- SOB, nausea, diaphoresis, light headedness
- lasts > 20 min but < 1 hour
- poor exs tol at baseline
clinical findings of unstable angina
- ischemic sx suggestive of ACS but no elevated troponins
- unstable plaque without rupture
- +/- ST depressions or nonspecific changes
clinical findings of NSTEMI
- ischemic sx suggestive of ACS
- elevated troponins
- unstable plaque +/- rupture
clinical findings of STEMI
- classic presentation
- plaque rupture with complete occlusion
initial management of chest pain
- vitals, EKG, cardiac monitor
- O2 if sat < 90%
- IV, bloodwork, CXR
- H&P
- ASA- 325 mg
- sublingual NTG q5 min X 3
- morphine for severe pain
- beta blockers within 24 hours
- anticoag- IV heparin cont infusion
- K and Mg
what is the TIMI risk score
- estimates 14 day mortality for pts with unstable angina/ NSTEMI
- low risk = score 0-2
- intermed risk= 3-4
- high risk = 5-7
indications for urgent angiography and revascularization
- hemodynamic instability or cardiogenic shock
- severe LV dysfunction or F
- recurrent or persistent rest angina despite intensive tx
- new or worsening mitral regurg
- sustained ventricular arrhythmias
requirements to be labeled STEMI
- > 2 mm St elevation in 2 contiguous precordial leads (1.5 in women)
- > 1 mm ST elevation in 2 contiguous other leads
- new LBBB in setting of acute chest pain is MI until proven otherwise
- often see reciprocal changes in opposite leads
anterior MI
- V2 V3 V4
- LAD
left lateral MI
- I aVL V5 V6
- left circumflex a
inferior MI
- II III aVF
- RCA
right ventricular MI
- aVR V1
- RCA
posterior MI
- ST depression in V2 V3 V4
- RCA
goal of tx of STEMI
- relieve chest pain
- correct abnormal hemodynamics
- initiate PCI within 90 min (120 min acceptable)
- if PCI unavail initiate fibrinolysis
- antithrombotic tx to prevent re-thrombosis or acute stent thrombosis
- BB to prevent recurrent ischemia and ventricular arrhythmias
fibrinolytic agents
- alteplase
- reteplase
- streptokinase
antithrombotic agents
- ticagrelor
- clopidogrel
- prasugrel
management of pts with acute STEMI
- acute triage
- activate cath lab -> PCI
- fibrinolytics if no PCI
- MONA
- O2 if sat < 90%
- BB
- high dose ASA
- K and Mg
- if pt found to have 3 vessel disease they skip PCI and get CABG
prinzmetal angina
- aka vasospastic angina
- d/t smooth muscle hyperreactivity
- angina sx at rest
- often between midnight and early morning
- assoc with transient (15 min) ST segment elevation, obstruction and myocardial ischemia
- possible MI
- triggered by coronary artery vasospasm
- usually dont have CAD
risk factors/ triggers for prinzmetal angina
- cigarette smoking
- genetics
- insulin resistance
- changes in autonomic activity- HR variability
- drugs- epi, cocaine, marijuana, alcohol, amphetamines
- Mg deficiency
vasospastic angina vs true STEMI
- pts usuall younger with vasospasm
- fam hx of prinzmetal
- few if any CV risk factors
- drug use
- repeat EKG in 15 min shows total resolution of ST segments
management of prinzmetal angina
- sublingual NTG during episodes
- smoking cessation
- long acting nitrates and CCB- prevent vasoconstriction and promote dilation
- statins
- Mg
- PCI with stent (rare)
