HYPERCHOLESTEROLEMIA AND DYSLIPIDEMIA

• Hypercholesterolemia


  Abnormally high level of blood cholesterol
• Dyslipidemia


  Abnormal levels of lipids in the blood
• Hyperlipidemia is a major cause of atherosclerosis and atherosclerosis-associated conditions, such as coronary heart disease (CHD), ischemic cerebrovascular disease, and peripheral vascular disease
• The incidence and absolute number of annual events will likely increase over the next decade because of the epidemic of obesity and the aging of the U.S. population
• Dyslipidemias, including hyperlipidemia (hypercholesterolemia) and low levels of high-density-lipoprotein cholesterol (HDL-C), are major causes of increased atherogenic risk
• Both genetic disorders and lifestyle (sedentary behavior and diets high in calories, saturated fat, and cholesterol) contribute to the dyslipidemias seen in developed countries around the world
• Lipoproteins


  Macromolecular assemblies that contain lipids and proteins
• Lipid constituents of lipoproteins


  • Free and esterified cholesterol
  • Triglycerides
  • Phospholipids
• Apolipoproteins/Apoproteins


  Protein components that provide structural stability to lipoproteins, and also may function as ligands in lipoprotein–receptor interactions or as cofactors in enzymatic processes that regulate lipoprotein metabolism
• In all spherical lipoproteins, the most water-insoluble lipids (cholesteryl esters and triglycerides) are core components, and the more polar, water-soluble components (apoproteins, phospholipids, and unesterified cholesterol) are located on the surface
• Major classes of lipoproteins

  • VLDL
  • IDL
  • LDL
  • HDL
  • Lp(a)
• Statins


  The most effective and best-tolerated agents for treating dyslipidemia
• Mechanism of action of statins

  Competitive inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, which catalyzes an early, rate limiting step in cholesterol biosynthesis
• Statins exert their major effect— reduction of LDL levels—through a mevalonic acid–like moiety that competitively inhibits HMG-CoA reductase
• By reducing the conversion of HMG-CoA to mevalonate, statins inhibit an early and rate-limiting step in cholesterol biosynthesis
• Statins affect blood cholesterol levels by inhibiting hepatic cholesterol synthesis, which results in increased expression of the LDL receptor gene
• The greater number of LDL receptors on the surface of hepatocytes results in increased removal of LDL from the blood, thereby lowering LDL-C levels
• Statins also can reduce LDL levels by enhancing the removal of LDL precursors (VLDL and IDL) and by decreasing hepatic VLDL production
• The reduction in hepatic VLDL production induced by statins is thought to be mediated by reduced synthesis of cholesterol, a required component of VLDL
• This mechanism also likely accounts for the triglyceride-lowering effect of statins and may account for the reduction (~25%) of LDL-C levels in patients with homozygous familial hypercholesterolemia treated with 80 mg of atorvastatin or simvastatin
• Acute myocardial infarction


  The medical name for a heart attack, refers to a heart condition that is caused when the blood circulation or flow is abruptly cut off from the heart
• Symptoms of heart attack

  • Anxiety
  • Cough
  • Dizziness
  • Fast heart rate
  • Heaviness in or across the chest
  • Pain in the chest, back, jaw, and other areas of the upper body
  • Shortness of breath
  • Sweating
  • Vomiting
• Risk factors for heart attack and atherosclerosis

  • An abnormally high level of blood cholesterol (hypercholesterolemia)
  • An abnormally low level of HDL (high-density lipoprotein), commonly called "good cholesterol"
  • High blood pressure (hypertension)
  • Diabetes
  • Family history of coronary artery disease at an early age
  • Cigarette smoking
  • Obesity
  • Physical inactivity (too little regular exercise)
• Diagnostic tests for heart attack

  • Electrocardiogram (EKG)
  • Physical examination
  • Blood tests for serum cardiac markers
  • Echocardiogram
• Preventive measures for heart attack

  • Exercising regularly
  • Eating healthfully
  • Maintaining a healthy weight
  • Not using tobacco products
  • Controlling your blood pressure
  • Lowering your LDL cholesterol
• Treatments for heart attack

  • Aspirin
  • Other medicines that help prevent unwanted blood clotting
  • Oxygen
  • Pain medication (usually morphine)
  • Beta-blockers
  • Nitroglycerin
  • Daily beta-blockers
  • ACE (angiotensin-converting enzyme) inhibitors
  • Cholesterol-lowering medication
  • Reperfusion therapy (mechanical or with thrombolytic agents)
  • Additional drugs to treat complications (e.g. arrhythmias, low blood pressure, congestive heart failure)