Unit 2 Day 5 (Mon 4/13) Flashcards Preview

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Flashcards in Unit 2 Day 5 (Mon 4/13) Deck (28):
1

CVD Prevalence

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

2

Steps in Atherosclerotic Process

-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

3

Lipid Metabolism- Exogenous

-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

4

Lipid Metabolism- Endogenous

-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

5

Statins

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

6

HDL

-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

7

Current Guidelines for Treating Blood Cholesterol

-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%

8

Hypertiglyceridemia

-associated with acute pancreatitis
-unclear whether lowering TG is beneficial

9

Why is inflammation implicated in atherogenesis?

-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

10

Monocyte Adhesion

-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

11

Adaptive Immunity in Atherogenesis

-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

12

Major Drivers of Plaque Instability

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

13

C Reactive Protein

-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

14

Role of Inflammation and Atherosclerosis

-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

15

Prevalence of Peripheral Vascular Disease and Risk Factors

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

16

Arterial Dynamics in PAD

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

17

Risk Factors for Abdominal Aortic Aneurysm

4 Major Risk Factors
-age
-gender (worse in men)
-smoking
-family history

18

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

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

19

Key Risk Factors that Initiate Aortic Dissection

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

20

Clinical Consequences of Aortic Dissection

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

21

Virchow's Triad

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

22

Heparin

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

23

Warfarin

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

24

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

-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"

25

Biologic and Behavioral Relationship Between Depression and CVD

-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

26

Screening and Treatment Strategies for Depression in CVD

-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

27

ankle-brachial index

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

28

Critical Leg Ischemia

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