CVD Pt II

What are two pathogenesis’ of atherothrombotic disease?

1. endothelial dysfunction

2. damage to vascular wall

What is endothelial dysfunction?

biochemical factors and functional changes which promote the development of atherosclerotic lesions

What are five biochemical factors which can promote the development of atherosclerotic lesions?

1. increased cytokines

2. increased adhesion molecules (attract immune cells)

3. increased growth factors

4. increased inflammation

5. decreased NO (NO by itself is important for contraction and relaxation of vascular wall)

What are two functional changes that can occur due to the biochemical factors that promote the development of atherosclerotic lesions?

1. vasoconstriction

2. platelet aggregation

What are atherosclerotic lesions?

related to the deposition of lipid within the vascular wall (fatty streak) and the development of a harder plaque and fibrosis around the fatty streak

What are three ways that we can get damage at the vascular wall?

1. stress of high BP

2. oxidation stress

3. inflammatory responses

Why is damage at the vascular wall bad?

monocytes are attracted to the damage

• bring lipids (such as LDL) which promote more oxidation and plaque buildup as a result of the oxidation

  • plaque can build up and break apart and have a thrombosis (clot)

What are the two main things regarding the cause of atherosclerosis?

1. LDL

2. Inflammation

used to think it was all LDL, however now know that inflammation is the main main driver

Characteristics surrounding LDL as the main causal factor of atherosclerosis.

• too much LDL circulating bc LDL receptor mediated uptake is too low

• LDL particles can traffic in and out of sub-endothelial spaces however its when they are retained through the sub-clinical oxidation process which is when its an issue (LDL is attracted by inflammation but is also a trigger for sub-clinical inflammation)

• LDL gets older and smaller and thus can squeeze between endothelial cells

Characteristics surrounding inflammation as the main causal factor of atherosclerosis.

• inflammation that can have multiple sources (excess adipose, GI tract, smoking)

• increases chronic levels of circulating cytokines and inflammatory mediators

• causes damage to endothelial wall due to presence of inflammatory meditators and sheer stress (high BP)

• old, small LDL get into sub-endothelial space, which are oxidized by immune cells already present

What are six promotors of plaque progression?

1. pro-inflammatory state

2. insulin resistance

3. elevated BP

4. atherogenic dyslipidemia (high blood circulating lipids)

5. pro-thrombotic sate

6. abdominal obesity

How do we know that LDL is not the primary cause of atherosclerosis/CVD?

• target for CHOL = < or equal to 100

• shows that CHOL is not the only factor; it is also other cardiometabolic factors (subclinical inflammation, high levels of glycemia, insulin resistance, BP, etc)

What is hyperlipidemia?

elevation of plasma lipids and lipoproteins

• cholesterol (Chol), chol esters (CE), triglycerides (TG), and apolipoproteins

What are four lipid panel measures that come from blood work?

1. total chol

2. HDL chol

3. TG directly

4. LDL chol (calculated from other values)

What equation is used to calculate LDL chol?

Friedwald equation

• LDL chol = tot chol - (HDL + (0.2 x TG))

• only valid when TG are within normal values

What are two commonly used lipid ratios?

1. total chol/HDL

2. LDL/HDL

Besides diet and PA, what are other factor can influence lipoprotein concentrations?

1. gene variation (can affect plasma lipoprotein concentrations and therapeutic response to diet modifications)

   1. there are many proteins that are genetically determined

What some genetically driven proteins that influence cardiovascular risk in terms of lipid levels? (5)

1. apoB

2. LDL receptor

3. apoE → several genotypes

4. apoA

5. Lp(a) → not modified by diet but genetically driven lipoprotein that is athrogenic