Unit 2 Day 5 (Mon 4/13)

Question 1

CVD Prevalence

Answer 1

• inc. with age

- initially most common in men, but as age inc. it becomes more common in women

Question 2

Steps in Atherosclerotic Process

Answer 2

• LDL infiltrates into sub endothelial space
• LDL is oxidized
• release of inflammatory cytokines and inc. expression of adhesion molecules
• monocytes recruited to clean up oxidized LDL
• phagocytosis of LDL leads to foam cell formation
• foam cells and T lymphocytes within plaque secrete MMP
• secretion and activation of tissue factors
• plaque rupture occurs in unstable lesions, leading to vessel thrombosis and acute coronary events

Question 3

Lipid Metabolism- Exogenous

Answer 3

• dietary
• processed into chylomicrons (E, C2, B48)
• LPL removes triglycerides from chylomicrons = remnant
• remnant binds to remnant receptor on liver
• taken up by liver and cleared from body

Question 4

Lipid Metabolism- Endogenous

Answer 4

• VLDL particles made by liver (proteins E, C2, B100)
• LPL removes triglycerids from VLDL to form smaller IDL
• IDL exposed to more LPL eventually forms LDL with only B100 protein
• LDL binds LDL receptor on liver

Question 5

Statins

Answer 5

-upregulate LDL receptor on liver to dec. LDL in bloodstream

Question 6

HDL

Answer 6

• removes cholesterol and replace with triglycerides
• CTP protein lowers HDL levels
• tries to remove cholesterol from body
• HDL is good
• under chronic inflammatory state, HDL may be no longer effective

Question 7

Current Guidelines for Treating Blood Cholesterol

Answer 7

• 4 major statin benefit groups
• individuals with known clinical ASCVD
• individuals with LDL >190 mg/dl
• individuals with diabetes (>40 yo and LDL >70)
• individuals (>40, LDL>70) w/o ASCVD or diabetes who have est. 10 yr ASCVD risk >7.5%

Question 8

Hypertiglyceridemia

Answer 8

• associated with acute pancreatitis

- unclear whether lowering TG is beneficial

Question 9

Why is inflammation implicated in atherogenesis?

Answer 9

• evolution of host response to bacterial infection inc. risk of sterile inflammation
• PAMPs
• DAMPs (oxidized LDL, cholesterol crystals)
• innate immune cell interaction with endothelium drives initial plaque formation

Question 10

Monocyte Adhesion

Answer 10

• VCAM1 on endothelium binds to CD11c and VLA4 on monocyte (oxidized LDL promotes expression of VCAM)
• adhesion is obligate step in atherosclerosis
• knocking out VLA-4 and CD 11c inhibits monocyte adhesion and limits atherosclerosis

Question 11

Adaptive Immunity in Atherogenesis

Answer 11

• dendritic cell presentation and subsequent T cell activation promotes T cell expansion
• Th1 response promotes IFNg elaboration and atherosclerosis
• Th17 may promote plaque instability
• T cells promote lesions expansion and plaque vulnerability

Question 12

Major Drivers of Plaque Instability

Answer 12

• Macrophage apoptosis and necrosis promotes a “necrotic core”
• Matrix metalloproteinases degrade the fibrous cap (secreted by macrophages)
• Intra-plaque hemorrhage further weakens core

Question 13

C Reactive Protein

Answer 13

• possibly expressed by macrophages and smooth muscle cells
• activates classical complement pathway
• high CRP-high LDL combined leads to dec. probability of event-free survival
• predicts excess risk of CV events after accounting for standard risk factors

Question 14

Role of Inflammation and Atherosclerosis

Answer 14

• impaired HDL efflux capacity associated with more psoriasis
• also related to RA
• inc. monocyte/macrophage activation: common mechanism underlying many autoimmune diseases
• tx of autoimmune disease may be associated with lower risk of CV events

Question 15

Prevalence of Peripheral Vascular Disease and Risk Factors

Answer 15

• adult prevalence = 10-20%
• risk factors: diabetes, smoking, lipids, hypertension
• PAD has 6x inc. risk of CV death

Question 16

Arterial Dynamics in PAD

Answer 16

• radius decreases
• flow rate inc. at stenosis and becomes turbulant
• however flow dec. relative to normal people in response to exercise
• blood viscosity inc.?

Question 17

Risk Factors for Abdominal Aortic Aneurysm

Answer 17

4 Major Risk Factors

• age
• gender (worse in men)
• smoking
• family history

Question 18

Risk of AAA Rupture in Relation to Size (diameter 5.0-

Answer 18

AAA diameter of 5-5.9 has a 25% 5 year rupture rate

Question 19

Key Risk Factors that Initiate Aortic Dissection

Answer 19

• hypertension (drugs ex. cocaine)
• inherited disorders of connective tissues (marfan, ehlers danlos)
• bicuspid aortic valve
• coarctation
• pregnancy
• aortitis
• iatrogenic (surgery, arterial catheterization)
• trauma

Question 20

Clinical Consequences of Aortic Dissection

Answer 20

• present with sever, tearing pain
• stroke (carotid)
• syncope (vertebral)
• myocardial infarction (coronary)
• intestinal ischemia (mesenteric vessels)
• renal failure (renal arteries)

Question 21

Virchow’s Triad

Answer 21

• abnormal flow (stasis)
• injury
• coagulation factors
• all of these can lead to thrombus

Question 22

Heparin

Answer 22

• parenteral
• directly binds antithrombin III, thus indirectly inhibiting factors II (thombin) and X
• factor Xa inhibitor

Question 23

Warfarin

Answer 23

• oral

- inhibits vitamin K dependent cofactors (II, VII, IX, X)

Question 24

Relationship between depression, cardiovascular disease (CVD) risk, and cardiovascular disease (CVD) outcomes.

Answer 24

• depression predicts incident of CV disease
• depression inc. risk of CAD by 1.5-2 times in otherwise physically healthy individuals
• depression predicts mortality after acute coronary syndrome
• “dose response relationship”

Question 25

Biologic and Behavioral Relationship Between Depression and CVD

Answer 25

- autonomic dysfunction - elevated cortisol - platelet activation - endothelial dysfunction - inflammation - defective serotonin signaling ultimately leads to inc. platelet activation (unifying hypothesis) - behavioral mechanisms: physical inactivity, lack of med adherence, lack of lifestyle changes, lack of self-management, lack of recommended testing, lack of follow up

Question 26

Screening and Treatment Strategies for Depression in CVD

Answer 26

- screening: two question screen, pt health questionnaire - tx: SSRIs, bupropion, cognitive behavior therapy, exercise training - tx must be coupled with education about expectations, structured follow up, dose adjustment, and additional health care if needed

Question 27

ankle-brachial index

Answer 27

- BPs from these locations should have 1:1 ratio | - ratio

Question 28

Critical Leg Ischemia

Answer 28

- severe PAD - may have ulcers - blanches if elevated - dependent rubor