W2 Cardiovascular Disease Flashcards
What are the non-modifiable risk factors of CVD? 3
What is not recommended for women
—genetics: concerning if male has MI <55 and female <65 (age is important!)
—age: increased risk for >45 for men and >55 for women
coronary fat streaks begin to develop in adolescence and then triples every decade!
—gender (men at greater risk but m/f same risk after menopause for women)
—HRT not recommended, doesn’t outweighs lifestyle benefits and may increase the risk of breast cancer, CHD, stroke and blood clots
What are the modifiable risk factors for CVD?
—diabetes
—HTN
—hyperlipidemia
—tobacco
—obesity, BMI
—physical activity
—diet
What are the biomarkers for CVD? 3
How else can you assess CVD?
—help stratify atherosclerotic risk and guide choice of therapies
—clinical measure to assess treatment effects
—potential targets of new therapeutic regimens
Examples
—C-reactive protein
—Vitamin D
—Plasma PCSK9
Little ability to improve outcomes aside from predicting individuals at higher risk of CAD/MI/stroke and PAD
ASCVD risk calculator on MDCalc
[SKILLS OSCE]
What is hypertension?
What is normal range?
What is elevated?
What are stage 1 and stage 2?
Hypertension is defined as: >130/>80
Normal: <120/80
Elevated: 120-129/<80
Stage 1: 130-139/80-89
Stage 2: >140/90
What is the normal A1C?
What is pre-diabetic
What is diabetic?
What does tight glucose control help?
Which newer drugs help?
Normal: <5.7%
Pre-diabetic: 5.7-6.4%
Diabetic: >6.5%
—Tight glucose control helps microvascular complications like retinopathy and nephropathy
DRUGS
—GLP-1 receptor agonists and SGLT2 inhibitors have macrovascular outcomes and reduce CV events of MI and CVA
Extra notes
—18.2 million people in the US and 170m worldwide
—1 in 3 kids born in 2000 will develop diabetes
—3-5x more likely to have an acute coronary event and 80% of diabetics die from atherosclerotic conditions including coronary disease, stroke or PAD
What is the goal BMI?
How much exercise
Which diet?
<24.9kg/m2
30 mins brisk walking a day
Mediterranean diet
DASH diet
But monitor calories, advise apps
Atherosclerosis
What is it?
What are the three walls of the artery?
Which layer:
—vaso vasorum
—produces inflammatory mediators?
—has smooth muscle cells
—maintains homeostasis
—prevents clotting
—synthesises elastin and collagen
—vasoconstriction/dilation
—contains nerves, lymphatics and blood vessels
—contains VSMCs
—controls passage of solutes
Atherosclerosis is a chronic inflammatory condition
Intima
Endothelium, simple squamous
Closest to lumen
Maintains homeostasis
Controls passage of solutes
Prevents clotting via antithrombotic molecules heparin/plasminogen
Anti-inflammatory at baseline but will respond to injury and stimulate an inflamm response
Media
Thickest later of smooth muscle that synthesise elastin and collagen from myofibroblasts for structural integrity under high pressure — constantly being remodelled
Vasoconstriction/dilates
Produces inflammatory mediators IL-1, TNF
Vascular smooth muscle cells (VSMCs)
Adventia
Contains nerves, lymphatics and blood vessels
contains vaso vasorum in the large elastic arteries
Nourishes the arterial wall via stem cells
Atherosclerosis
What is the fatty streak stage?
What 4 processes are happening and what are the driving factors for them?
When does it develop?
Develops in adolescence
Branch points — lipids — leukocytes — foam cells
-
Endothelial dysfunction
—branch points in the vessel favour athermoma, while straight sections are protected by NO, anti-platelet and anti-inflamm markers. Also less stress along the straights.
—toxic chemicals (tobacco, elevated lipids, diabetes) -
Accumulation of lipids within the intima
—LDL binds to proteoglycans and is trapped. This is enhanced by HTN and DM
—oxidation also modifies LDL and maintains it in the subendothelial space -
Recruitment of leukocytes
—monocytes and T lymphocytes -
Formation of foam cells
—type of macrophage that localises to fatty deposits on blood vessel walls
—ingest lipoproteins and accumulate in plaque
—smooth muscle cells secrete collagen and EARLY plaque grows outward from the arterial wall preserving diameter of the lumen.
No flow limiting lesions and not detected on angiography
Atherosclerosis
What is the plaque progression stage?
What is a stable plaque?
What is a vulnerable plaque?
Deposition of the Extracellular matrix:
—smooth muscle cells migrate into the intima from the media increasing the bulk of the lesion and restricting the lumen of the vessel, impeding perfusion
—fibrous cap develops to preserve integrity of the plaque
—small non occlusive thrombi can occur and incorporate into the plaque
Synthesis and degradation continues for decades.
As the lipid core grows in size and protrudes into the arterial lumen, it is susceptible to more mechanical stress forces
Thicker fibrous caps (stable plaque) are less likely to rupture than thin fibrous caps (vulnerable plaque)
Describe these complications of atherosclerosis
Calcification
Rupture
Haemorrhage
Embolisation
Aneurysm
Calcification — creates more vulnerable plaque and can lead to rupture
Rupture — of the plaque exposes procoagulants to circulating blood causing a thrombus to form. Can lead to vasoocclusion and infarction. Thrombus can also incorporate into the lesion and add to the size of the plaque
Haemorrhage — into the plaque due to micro vessel rupture can lead to an intramural hematoma and narrow the vessel lumen
Embolisation — of fragments of the plaque to distal vascular sites
Aneurysm — weakening of the vessel wall from increased pressure from the plaque to the neighbouring medial layer. Causes loss of elastic tissue and subsequent expansion of the artery forming an aneurysm
What are the five major lipoproteins
What do they do?
Which is the most concerning?
Which is not on a standard lipid panel?
Transport cholesterol and triglycerides in the blood
LDL = actual mortality benefit
— correlates to an increase incidence of atherosclerosis or CAD
—there is a genetic abnormality in the LDL receptor clearance mechanism that allows LDL to accumulate in circulation
HDL
— “good cholesterol” — protects against atherosclerosis by transporting cholesterol away from the peripheral tissues back to the liver for disposal. It has antioxidative and anti-inflammatory properties
VLDL — casual role in atherosclerosis
IDL — casual role in atherosclerosis
Chylomicrons
Lipoprotein (a)
—is identical to LDL except the addition of apolipoprotein A. Detrimental effect thought to be related to delivering cholesterol to damaged endothelial cells to restore membranes
—Lipoprotein (a) is not on a standard lipid panel FYI.
—It thinks it’s restoring the damaged endothelial cells but it’s just bringing more LDL
[SKILLS OSCE]
What is the recommendation for a fasting lipid panel?
What lifestyle modifications can be made?
What is an abnormal lipid panel? (Total, LDL, HDL, triglycerides)
Every 5 years for adults >20 y/o
Weight loss, change diet to unsaturated fats, increase fibre, plant stanols, increased physical activity
Total cholesterol >200 mg/dL
LDL >130 mg/dL
HDL <40 mg/dL in men / <50 mg/dL in women
Triglycerides > 150 mg/dL
What do statins do?
Which examples for high intensity, moderate and low?
They treat hyperlipidemia
High: lower LDL by 50% or more
—Atorvastatin 40-80mg
—or Rosuvastatin 20-40mg
Moderate lowers by 30-49%
—Atorvastatin 10-20mg
—or Rosuvastatin 5-10mg
—Simvastatin 20-40mg
—or Pravastatin 40-80mg
Low intensity lower <30%
—Simvastatin 10mg
—or Pravastatin 10-20mg
pravastatin is well tolerated and has fewer side effects
See attached table
R
A
S
P
What are the 4 main groups (candidates for) of statin therapy? [know]
- Individuals with clinical ASCVD
- Individuals with elevations of LDL >190 OR familial hyper cholesterolemia
- Individuals 40-75 y/o with diabetes and LDL 70-189
- Individuals WITHOUT ASCVD or DIABETES who are 40-75 years of age with LDL levels 70-189 and an estimated 10 year ASCVD risk of 7.5% or higher
ASCVD = atherosclerotic cardiovascular disease
Additional groups who could benefit from statin therapy
Use your clinical judgement here
LDL >160 is very high!
Hyperlipidemia
If lifestyle modifications fail, what are the 3 main pharm therapies?
Remember statins are king! Still the first line pharm therapy
2nd: ezetimibe
3rd: PCSK9
Lipid lowering medications
How do PCSK9 inhibitors work?
they reduce degradation of LDL receptors thus reducing circulation of LDL
Lipid lowering medications
How do statins work? 2
Reduction average?
What are their pleiotropic effects ? 3
What are their side effects? 3
—inhibit the rate limiting enzyme responsible for cholesterol biosynthesis.
—resulting reduction in intracellular cholesterol concentration promotors the increased LDL receptor expression which results in augmented clearance of LDL from the blood.
—reduction averages 20-60%
Pleiotropic effects:
—improvement in endothelial dysfunction
—antioxidant and anti-inflammatory properties
—plaque stabilisation by reducing lipid content
mortality benefits, high efficacy means statins are still first line agent for hyperlipidemia
S/E
—elevations in LFTs > should be discontinuied when there is a > than a threefold elevation
—myopathies
—drug interactions (+ CYP)
Lipid lowering medications
How do cholesterol absorption inhibitors work? 4 points
What is the LDL reduction
Who are they for?
cholesterol absorption inhibitor
—selective inhibitor of cholesterol uptake at the brush border of the epithelial cells in the small intestine.
—reduced chylomicron production
—less cholesterol delivered to the liver
—stimulates hepatic production of LDL receptors which clear the blood of LDL
LDL reduction ~18%
Main use: LDL lowering in statin tolerant patients or for patients who require additional LDL reduction already on max dose statin.
Lipid lowering medications
How do Proprotein Convertase Subtilising/Kexin Type 9 Inhibitors work (PCSK9)
—what does PCSK9 normally do?
—what do PCSK9 inhibitors do?
—name two monoclonal abs aimed at PCSK9
—PCSK9 binds to LDL receptors and target is for lysosomal destruction rather than recycle it which impairs LDL removal from circulation
—PCSK9 inhibitors prevent this thereby manifesting more LDL receptors and increased LDL removal from the blood
—Alirocumab and Evolocumab are monoclonal abs directed against PCSK9 and can reduce LDL by 50-60% when added to statin therapy. Trials show a reduction in CV events, including death, when combined with statin therapy after ACS or with underlying atherosclerotic disease.
—current indication patients with atherosclerotic disease and or familial hypercholesterolemai with elevated LDL levels on max statin plus ezetimibe (which is an intestinal cholesterol absorption inhibitor)
Lipid lowering medications
How do bile acid sequestrants work?
LDL reduction?
Poorly tolerated why?
—blocks bile acid in your stomach from being absorbed into the blood.
—the liver then uses the cholesterol from your blood to make more bile acids, thus lowering cholesterol level.
—LDL reduction in 15-30%
—poorly tolerated due to constipation
Lipid lowering medications
How does Nicotinic Acid/Niacin work?
Reduction level?
What else can it lower?
Why poorly tolerated?
—decreases fatty acid mobilisation from adipose tissue
—and reduces synthesis of LDL and VLDL
—affects all lipid parameters favourable with LDL reduction of 5-25%, triglyceride reduction 20-50% and HDL elevation of up to 15-35%
—able to lower lipoprotein (a)
—very poorly tolerated due to side effects including flushing, pruritus, and GI disturbances
Lipid lowering medications
How do fibrates work?
What do they reduce?
By how much?
—increases lipoprotein lipases responsible for lipolysis
—most effective at reducing triglyceride levels —has a 20-50% lowering effect
—lowers LDL by 5-20% and increases HDL
Fenofibrate is the safer medication to use if needed
Estrogen status & CAD — what do we know?
Prior to menopause, estrogen exerts atheroprotective properties — this led to the creation of HRT
They realised that the benefits were not necessarily related to HRT but rather the lifestyles of the people taking HRT rather than the medical benefits
What are the updated cholesterol guidelines [know]
What is the main goal now?
What is the recommended therapy for low, borderline, intermediate and high?
lower is better
aim for % decrease
—low risk <5% = lifestyle improvements
—borderline 5-7.5% = consider moderate intensity statin
—intermediate 7.5 - 20% = consider moderate intensity statin to reduce LDL by >30%
—if ineffective, consider adding ezetimibe or bile acid sequestrant
—high >20% = moderate/high intensity statin to achieve >50% reduction in LDL
What is familial hypercholesterolemia?
Genetic abnormality in the LDL receptor clearance mechanism that allows LDL to accumulate in the circulation since it cannot be removed. It can be heterozygous or homozygous
These patients will have a propensity to develop early onset CAD/Ischemic.
Statins don’t work on these patients
Guideline recommendations for lipid altering therapy (must know)
ASCVD
—high intensity statin: >50 LDL reduction
—if remains high, add ezetimibe
—if remains high still, add PCSK9 inhibitor
LDL >190
—high intensity statin: >50 LDL reduction
—if remains high, add ezetimibe
—if remains high still, add bile acid sequestrant
Diabetes
—age 40-75
—regardless ASCVD risk
—moderate statin for >30% reduction
—high intensity statin for >50% reduction
—+ezetimibe
Ezetimibe — a cholesterol absorption inhibitor that targets uptake at the jejunal enterocyte brush border
Bile acid sequestrants — These medicines work by blocking bile acid in your stomach from being absorbed in your blood. Your liver then needs the cholesterol from your blood to make more bile acid. This reduces your cholesterol level
What is the rule of 6s with statin dosing?
if the dose of a statin is doubled then there is an approximate 6% increase in LDL lowering efficacy by doubling the dose - the so-called 6 percent rule
How for you calculate BP?
How do you calculate CO?
[know these]
BP = cardiac output x total peripheral resistance
CO = volume of blood ejected from the ventricular per minute, ~5 litres
CO= stroke volume x HR
SV = volume of blood ejected from ventricle during systole
SV depends on preload, afterload, and cardiac contractility
Stroke volume is the combination of what three things ? +/-
+contractility
+preload (like the gas tank)
- afterload (what the LV is pushing against)
Hypertension
4 systems regulate BP
- Heart: pumping pressure/contractility
- Vascular/vessel tone: determines peripheral resistance
- Kidney: regulates intra vascular volume and peripheral resistance
no matter how high the cardiac output or total peripheral resistance, renal excretion or volume can return BP to normal
pressure natriuresis (urine volume and sodium excretion) is blunted in HTN due to microvascular and tubulointerstitial injury
- Hormones : module the functions of the other systems: RAS, adrenal hormones and CNS catecholamines
HTN system activated by?
Located where?
baroreceptor reflex
Located in aortic arch and carotid sinuses
Not involved in long term regulation or prevention of chronic HTN as the baroreceptor reset themselves to high pressures and inhibit feedback.
Learn the RAS system
What is “essential HTN”
What could be causing it?
How do you confirm the diagnosis?
What is it called if there is an underlying cause?
“Essential HTN” = 90% of patients! We don’t know what’s causing it
—genetics
—environmental
—behavioural factors
need two separate visits AND and ambulatory blood pressure monitor at home to confirm the diagnosis (white coat syndrome)
10% has an underlying cause, this is known as “secondary HTN”
Essential HTN
—genetics
No singular genetic marker for HTN has been discovered, likely a complex, polygenic disorder
—environmental
High sodium diet, alcohol intake, poor exercise
—systemic abnormalities
RAAS dysfunction in kidney/adrenal catecholamine mal regulation
Abnormal stress response or increased basal sympathetic tone in the CNS
Blood vessel hyper responsiveness to catecholamines/increased endothelial
—insulin resistance and obesity
—increases sympathetic activation
—increased vasc resistance
—obesity increases blood volume related to increased body mass and blood viscosity
—natural history or age
—younger people have higher BP
—as age, CO declines and vascular resistance increases from hypertrophy related to prolonged pressure stress
Essential HTN — secondary causes
Exogenous
Renal
Exogenous:
—prescribed: OCPs, NSAIDs, epogen
—recreational stimulate use and chronic alcohol consumption/withdrawal
Renal causes:
—renal artery stenosis > atherosclerosis and fibromuscluar dysplasia reduces renal blood flow therapy secreting renin secondary to low perfusion
—CKD > damaged nephrons are unable to excrete normal amounts of Na and H2O leading to a rise in intravascular volume, elevated CO, and increased BP
HTN — secondary causes
Mechanical
Endocrine - 6
Mechanical
—coarctation of the aorta: congenital narrowing of the aorta causing low perfusion to kidney and activation of RAAS as well as elevated pressures proximal to the stenosis blunting the baroreceptor reflex.
—finding on CXR: rib notching
Endocrine
—pheochromocytoma: catecholamines secreting tumours on the adrenal medulla
—adrenal cortex hormone excess: mineralocorticoids (hyperaldosteronism) and glucocorticoids (Cushing syndrome)
—mineralocorticoids: primarily aldosterone, increase blood volume by augmenting reabsorption of sodium in exchange for potassium excretion (hypokalemia)
—glucocorticoids: mostly cortisol, elevated BP via volume expansion and sodium retention
—hyperthryroidism: cardiac hyperactivity from sympathetic stimulation with an inc in blood volume
—obstructive sleep apnea: sympathetic spikes during apneic period
HTN: secondary causes
Also consider work up it?
Age : before 20y/o and after 50y/o
Severity: dramatic right or refractory to multi drug regimen
Onset: abrupt presentation in someone who was normotensive
Associated signs/symptoms : renal artery bruits eg
Family history : essential HTN often has 1st degree relatives, secondary is more spontaneous
Causes of HTN 7
—most cases are essential HTN 90%
Other causes
—chronic renal disease
—primary aldosteronism
—renovascular
—pheochromocytoma (A hormone-secreting tumor that can occur in the adrenal glands)
—coarctation of the aorta
—Cushing syndrome
HTN: consequences
—generally asymptomatic
—LVH, heart failure, MI, Ischemic
—cerebri vascular > stroke
—aorta & peripheral vascular > aneurysm, dissection and atherosclerosis
—kidney > nephrosclerosis and renal failure
—retina > arterial narrowing, haemorrhages,exudates, papilledema
HTN on PE
Eyes, neck, heart, abdomen, extremities?
—fundoscopic for retinopathy (disk edema, hemorrhages, arteriolar narrowing)
—neck for JVD, bruits, goiter
—heart for murmurs, gallops
—abdomen for bruits and central obesity
—extremities for diminished or absent pulses, hair loss, edema
HTN diagnostics
What other tests can you run?n5
—UA especially for proteinuria
—A1C, lipid panel, TSH, chemistry panel, CBC
—EKG for arrhythmias and LVH
—echo to assess for structure heart disease
—possible renal u/s, thyroid u/s
HTN: treatment
What do you recommend first?
When should therapy be initiated?
When do you add a second agent?
When at goal, how often do you assess?
—lifestyle modifications first
—Start if the pressure is >130/80 mmHg especially if the patient has CAD risk factors
—if the pressure is >20/10mmHg over goal after initial therapy, then likely two agents will be needed
—re-check pressure after one month. If not at goal (120/80), titration dose or add second agent. Once at goal, assess every 3-6 months
HTN: what are the choices of medication? 4 main ones
What are the rest?
Consider: concomitant diseases, cost, race, and drug-drug interactions
Main classes
—thiazide diuretics
—calcium channel blockers
—ace inhibitors or ARB
—beta blocker: 4th line agent, not as effective. Side effects in younger people, fatigue. Very useful in pts who have had an MI, good for CAD.
The rest:
—loop diuretics: mostly used for heart failure, volume overload situations
—mineralocorticoids receptor antagonist (aldosterone)
—alpha blockers (terazosin)
—central alpha-2 agonists (colonising, methyldopa)
—direct vasodilators (minoxidil, hydralazine)
What is the MOA for these HTN drugs?
Diuretics
Sympatheolytics
Vasodilators
Renin-angiotensin system antagonists
Diuretics: reduce circulating volume
Sympatheolytics: reduce HR, cardiac contractility, renin secretion.
Decrease sympathetic tone
Vasodilators: reduce vascular resistance
Renin-angiotensin system antagonists (ACEI/ARB)
HTN emergency vs urgency
[know]
Severe blood pressure is :
180/120
Emergency is defined as severe blood pressure WITH end organ damage — look at labs. End organ damage could be high troponin, pulmonary edema, papilledema, renal failure
Urgency: severe BP without end organ damage
HTN + end organ damage
What does end organ damage include? 5
Brain: encephalopathy or signs of stroke/intra cerebral haemorrhage (CT scan)
Eye: retinopathy (fund.exam)
Evidence of damage to heart including Ischemia: troponin leak, EKG changes
And heart failure (echo to assess LV< chest XRay and BNP for pulmonary edema and elevated JVP)
Renal damage as eveidenced by elevated creatinine or proteinuria/hematuria
Aortic dissection
Causes of emergency HTN 6
—undiagnosed essential HTN and initial visit
—non-adherence to anti-HTN and rebound effect
—street drugs
—CKD
—secondary HTN causes including renal artery stenosis and pheochromocytoma (small vascular tumour of the adrenal medulla causing irregular secretion of epinephrine and norepinephrine leading to attacks of raised BP, palpitations and headaches)
—sleep apnea
Treatment for emergency HTN
What are the goals in terms of MAP and BP?
Not the same as for essential HTN!
Require IV meds: including CCV, BB, nitrates, direct vasodilators and ICU level of care. Don’t want to drop it too quickly because those organ systems have been used to that pressure for a while. So it can cause Ischemic or stroke if you drop too quickly (hypoperfusion)
Goals:
—reduce MAP (SBP+2/DBP/3) which is the average arterial blood pressure over one cardiac cycle by no more than 25% in the first few hours (know this for critical care!)
—if stable, lower to a goal of 160/100 within the next 2-6 hours followed by adding oral agents and wean off IV meds
Cardiac risk assessment
slides 83-91
Said he won’t test us so just read through if you want
