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Angina (Risk factors (Hypertension, Diabetes Mellitus, Obesity, Family…

- - - - Endothelial dysfunction and injury around sites of sheer and damage with subsequent lipid accumulation at sites of impaired endothelial barrier
      - Local cellular proliferation and incorporation of oxidise lipoproteins occurs
      - Mural thrombi on surface and subsequent healing and repeat of cycle
    - - As plaque progresses to 50% of vascular lumen size, the vessel can no longer compensate by remodelling and becomes narrowed
      - This drives variable cell turnover within the plaque with new matrix surfaces and degradation of matrix
      - May progress to unstable plaque
    - - This drives an inflammatory reaction against part of the plaque contents
      - Complications develop including ulceration, fissuring, calcification and aneurysm change
      - The plaque continues to encroach upon the lumen and runs the risk of haemorrhage or exposure of tissue HLA-DR antigens which might stimulate T cell accumulation
    - - Intimal cell mass
        
        Collections of muscle cells and connective tissue without lipid - 'cushions'
      - The atheromatous plaque
        
        Distorted endothelial surface containing lymphocytes, macrophages, smooth muscle cells and variably complete endothelial surface
        
        Local necrotic and fatty matter with scattered lipid rich macrophages
      - Fatty streak
        
        Macrophages filled with abundant lipid (foam cells)
        
        Also smooth muscle cells with fat
      - Complications of plaque rupture
        
        Acute occlusion due to thrombus
        
        Chronic narrowing of vessel lumen with healing of the local thrombus
        
        Aneurysm change
        
        Embolism of thrombus +/- plaque lipid content
- - - - Thus reduces after load on the heart
      - Thus less energy required to produce same cardiac output
      - Dilates systemic arteries resulting in BP drop
      - Thus less work on the heart and O2 demand
      - Primary arterodilators
      - Example is verapamil
    - - Examples include bisoprolol and atenolol
      - Act on beta 1 receptors in the heart as part of the adrenergic sympathetic pathway
      - Reduces force of contraction of heart
      - B1 activation - Gs - cAMP to ATP - contraction
      - Reduces:
        
        Heart rate (negatively chronotropic)
        
        Left ventricle contractility (negatively inotropic)
        
        Cardiac output
      - Side effects: tiredness, nightmares, bradycardia, erectile dysfunction and cold peripheries
      - DO NOT GIVE in asthma, heart failure/heart block, hypotension and bradyarrhythmias
    - - Dilates systemic veins thereby reducing venous return to right heart
      - Reduces preload
      - Nitrate that is a venodilator
      - Thus reduces work of heart and O2 demand
      - Also dilates coronary arteries
      - Side effect: profuse headache immediately after use
    - - Reduce events and LDL-cholesterol
      - Anti-atherosclertoic
      - HMG-CoA reductase inhibitors - reduces cholesterol produced by liver
    - - Used to reduce events occurring
      - Examples - salicylate
      - Antiplatelet effect (inhibits platelet aggregation) in coronary arteries thereby avoiding platelet thrombosis
      - COX inhibitor - reduces prostaglandin synthesis including thromboxane A2 resulting in reduced platelet aggregation
      - Side effects - gastric ulceration
  - - - Dilating coronary atheromatous obstructions by inflating balloon within it
      - Insert balloon and stent, inflate balloon and remove it, stent persists and keeps artery patent
      - Expanding plaque = make artery bigger
      - Pros: less invasive, convenient, short recovery and repeatable
      - Cons: risk of stent thrombosis, not good for complex disease
    - - Pros: good prognosis, deals with complex disease
      - Cons: invasive, risk of stroke or bleeding, one time treatment and need to stay in hospital - long recovery
      - Left Internal Mammary Artery (LIMA) used to bypass proximal stenosis (narrowing) in LAD coronary artery