Lecture 16: Risk Factors and Lipids Flashcards
What two cell types maintain integrity/elasticity of arterial vasculature?
Endothelial cells and smooth muscle cells
Endothelial cells = normal function
Impermeable (to large molecules, like LDL-C), anti-inflammatory, promote vasodilation, resist thrombosis
Smooth muscle = normal function
Cause vasoconstriction/dilation, produce extracellular matrix to maintain vascular integrity (collagen and elastin)
What is the first step of atherosclerosis
Endothelial cell dysfunction = particles (e.g. LDL) allowed into subendothelial space
What is the second step of atherosclerosis
Recruitment of immunologic mediators. This actually causes more LDL to be deposited
What happens to the LDL?
Modification –> oxidation/glycation
What happens to immune cells?
Uptake of mLDL by monocytes –> “foam cells”
All of the above leads to the formation of __________. When does this happen?
Lesions! Late teans
What happens to the smooth muscle cells?
Smooth muscle cell migration across the tunica intima into the plaque
Three key features of atherosclerotic lesions
- Fibrous cap; 2. Lipid material (cholesterol); 3. Inflammation
Two atherosclerotic categories and features
Vulnerable plaque: large lipid core, thin fibrous cap, many inflammatory cells; Stable plaque: small lipid pool, thick fibrous cap, preserved arterial lumen
What happens if a fibrous plaque breaks open?
Released cholesterol can cause blood to clot –> thrombus
What is the most common mechanism for an atherosclerotic-induced MI?
Fibrous cap rupture
What is another (besides MI) consequence of a ruptured fibrous cap?
Healed rupture = narrow lumen and fibrous intima
Traditional risk factors for atherosclerosis (two categories: 3, 4)
Non-modifiable: age, sex, family history; modifiable: dyslipidemia, smoking, DM, physical inactivity
Non-traditional risk factors for atherosclerosis (3)
Apoplipoprotein, c-reactive protein, homocysteine
Density of lipoprotein increases as the ratio of…
Protein/lipid increases (LDL = more cholesterol)
HDL-C (describe)
“Good cholesterol” = reverse cholesterol transport by scavenging for deposited cholesterol from periphery to liver
LDL-C (describe)
“Bad cholesterol” = deposits cholesterol into arterial walls, target of pharmacotherapy
T/F: Diet and exercise can help lower LDL-C
True
Four classes of LDL-C lowering pharm agents
Niacin, bile acid seqestrants, fibric acid, statins
What are statins?
HMG-CoA Reductase Inhibitors = increased expression of LDL-C receptor in liver, lowering serum LDL-C
Other benefits of statins (4)
Modest raise in HDL-C, favorably modulate vascular tone, stabilize plaque, reduce inflammation
Major risk factors for coronary heart disease (5)
Cigarette smoking, HT, low HDL, family history of premature CHD (male relative 45, females >55)
If 10-year risk of a heart attack is higher than _____% prescribe…
7.5%; statins
Are there current pharm agents to raise HDL-C?
No: due to SEs and toxicity
What is one way to raise HDL modestly?
Statins, niacin
What is the best way to raise HDL?
Diet and exercise
Cardiovascular effects of DM (5) which lead to…(2)
Enhanced inflammation, hypercoagulability, endothelial dysfunction, glycation of lipoproteins, vascular stiffness/calcification –> accelerated atherosclerosis and prothrombotic state
By how much does diabetes increase risk for CVD?
Men: 8 –> 17%; Women: 4 –> 17%
All diabetic patients should be treated for…why?
Heart disease; patients with diabetes with no prior heart attack are at the same risk for a heart attack as a non-diabetic patient with a prior heart attack
How do we treat patients with diabetes to reduce macrovascular risk?
Control: blood pressure, lipids, obesity (controlling glucose does not decrease risk)
Describe obesity and vascular effects (4)
- Inflammation = adipose releases pro-inflammatory cytokines; 2. Hypertension due to increased CO; 3. Endothelial dysfunction; 4. Insulin resistance
What are the current physical activity recommendations?
30 minutes or more of moderate activity on most days
Smoking related mechanisms of injury (4)
Endothelial damage, prothrombotic effects on platelet function, coronary vasoconstriction, oxidative modification of LDL-C
Describe homocysteine’s role in atherogenesis
Elevated homocysteine linked to pathophysiology of atherosclerosis but lowering does not help
Describe lipoportein (a)’s role in atherogenesis
Higher levels of lipoprotein (a) associated with higher CV risk but not good therapies
Describe c-reative protein’s (CRP) role in atherogenesis
Maker of inflammation, statin therapy might lower CRP (prescribe even if there LDL-C is not high)
