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)
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
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)
Learn the RAS system
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
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)
