Atherosclerosis

• Atherosclerosis is a syndrome affecting large and medium-sized arteries
• It involves artery wall thickenings, lipid infiltration, and atheroma creation
• Chronic inflammatory response occurs in the walls of arteries
• Resulting in hardening of the artery wall (loss of elasticity) and insufficient blood supply
• Insufficient blood supply can lead to myocardial infarction (heart attack), stroke, or claudication
• Theories of atherosclerosis:

  • Lipid theory: Primary is the accumulation of lipids in the vessel wall
  • Endothelial damage theory: Primary is the damage of the endothelium
  • United theory: Primary is endothelial damage leading to inflammation, macrophages phagocytizing lipids, and atherosclerotic plaques
  • Infectious theory: Primary is damage of the endothelium caused by bacterial or viral infection
• Stages of atherosclerotic plaque development:

  • I: Isolated foam cells - macrophages with a droplet of fat in intima
  • II: Fatty streaks - foam cells layer
  • III: Intermediate atheroma - higher amount of lipids under the foam cells layer
  • IV: Atheroma - lipid core, fibrous cap
  • V: Fibrotic atheroma - more collagen and smooth muscle cells in fibrous cap
  • VI: Complicated atheroma (vulnerable plaque) - atheroma with complications like thrombosis
• Stable vs. unstable atherosclerotic plaque:

  • Stable plaque has a small lipid core, thick and stable fibrous cap, and lower rupture tendency
  • Unstable (vulnerable) plaque has a big lipid core, thin fibrous cap, high rupture and thrombosis probability, high erosion probability, and high calcification probability
  • Rupture is caused by inflammatory cells like macrophages and neutrophils, leading to acute coronary syndrome
• Risk factors for atherosclerosis:

  • Basic biological factors: Age, gender, family history, genetic risk factors
  • Biochemical factors: Cholesterol levels, lipoproteins, new biochemical markers like homocysteine and ferritin
  • Nutrition and lifestyle: Diet high in fat and sugar, antioxidant and fiber deficiency, smoking, sedentary lifestyle
  • Diseases: Obesity, diabetes mellitus, hypertension, kidney failure
• Metabolic syndrome:

  • Combination of medical disorders increasing the risk of cardiovascular disease and diabetes
  • Signs include fasting hyperglycemia, high blood pressure, central obesity, decreased HDL cholesterol, and elevated triglycerides
  • New classification includes criteria like abdominal obesity, elevated triglycerides, reduced HDL-cholesterol, elevated blood pressure, and elevated fasting glucose
• Lipoproteins:

  • Chylomicrons: Produced by enterocytes, transport lipids from the diet, and are cytotoxic and atherogenic
  • VLDL - LDL family: Produced by the liver, transport endogenous TAG and cholesterol, and can be modified leading to atherosclerosis
  • HDL: Reverse transports cholesterol, produced by the liver, and plays a role in cholesterol metabolism
• Familial hypercholesterolemia:

  • Inherited disorder with symptoms like increased LDL cholesterol concentration and a high risk of atherosclerosis and myocardial infarction
  • Can be heterozygous or homozygous, with different levels of LDL concentration and severity of symptoms
• Other new biochemical risk factors:

  • Small dense LDL: Small, dense, and easily oxidized leading to a higher risk of atherosclerosis
  • Lipoprotein(a): LDL with apoprotein(a) associated with a higher risk of thrombosis
  • Oxidized LDL (oxLDL): Highly atherogenic and has a higher affinity for macrophages
• Genetic factors:

  • Apolipoprotein E: Different alleles with varying risks for high cholesterol and complications of atherosclerosis
  • Homocysteine, ferritin, and fibrinogen: New biochemical markers associated with oxidative stress, inflammation, and coagulation
• Lifestyle factors:

  • Smoking: Nicotine and CO affect lipid metabolism, vasoconstriction, and coagulation cascade activity
  • Obesity: Visceral obesity leads to insulin resistance, dyslipidemia, and atherosclerosis
  • Diseases like diabetes mellitus, kidney diseases, and liver diseases can also contribute to atherosclerosis
• Metabolism of lipoproteins:

  • Normal values for total cholesterol, HDL cholesterol, LDL cholesterol, and triglycerides
  • Various indexes used to assess the risk of atherosclerosis based on lipid profiles and apolipoproteins
• Hyperlipoproteinemias:

  • Primary and secondary causes of high cholesterol and triglyceride levels, including genetic disorders and lifestyle factors
  • Symptoms and signs include xanthomas, arcus lipoides corneae, xanthelasma palpebrarum, and atherosclerosis