Overview and Risk Factors for Atherosclerosis

Overview and Definitions

• Atherosclerosis is one of three types of arteriosclerosis, or hardening of the arteries.
  • The other major type is ateriolosclerosis, discussed the other day during the discussion of benign and malignant hypertension (hyaline and hyperplastic arteriolosclerosis respectively).
• Greek origin is from gruel (athero) and hardening (sclerosis).
  • For those not in the know, gruel is porridge or oatmeal. So digitally palpated atherosclerosis is gritty, lumpy bumpy hard stuff.
• Atherosclerosis is silent and progressive. You don’t know you’re getting it because you can’t feel anything happening.
  • Even 1 year old babies have been shown to have the earliest stage of the disease known as fatty streaks.
  • These lesions will develop and eventually progress to symptomatic disease later in life (normally the 50s and 60s).
• Atherosclerosis affects many different vessels in the body.
  • The aorta can harden leading to abdominal aortic aneurysms and aortic dissections.
  • Coronary arteries can be involved, causing ischemic heart syndrome which leads to myocardial infarction.
  • Cerebral arteries involved can lead to cerebrovascular disease, transient ischemic attacks, brain infarcts, and intracerebral hemorrhage or stroke.
  • Popliteal artery involvement will result in gangrene and peripheral vascular disease of the legs.
• Like all vasculitites (temporal arteritis, e.g.) Atherosclerosis targets certain types and sizes of vessels preferentially.
  • The elastic arteries and the large and medium-sized arteries are most affected by Atherosclerosis (only arteries)
    • Not small arteries or arterioles.
• Because atherosclerosis is a silent disease, you cannot assess it clinically. The only epidemiology of atherosclerosis is that associated with the problems it causes, such as stroke and MI.
  
   

Risk Factors

• Risk factors are various and can be divided into two main categories.
  • Constitutional factors are those that can’t be helped. They are things you’re born with. These are predominantly genetic problems.
  • Acquired factors are those that you develop during life and can be changed. You can modify your diet and activity level, for example.
• Constitutional factors include inherited disorders like:

• Familial hypercholesterolemia. We covered this one quite a bit last year with MGM so think way back (and thank me when it comes to board prep).
  • This is a very common autosomal dominant disorder with 1 in 500 zygotes in the general population carrying the disease.
  • It is characterized by very high serum cholesterol levels and hyperlipidemia (which is also an acquired risk factor for Atherosclerosis).
• Homocysteinuria is a genetic disorder (not really covered here) that also leads to a hyperhomocysteinemia, yet another acquired risk factor for Atherosclerosis.
• Other, non-disease constitutional risk factors listed on the outline but not mentioned in class are age (older is worse), sex (male is worse than female until the age of 65), and family history of MI in a parent or sibling under the age of 55.

• Acquired risk factors include:
  • Hyperlipidemia, particularly hypercholesterolemia and to a lesser extent hypertriglyceridemia.
    • Low density lipoprotein (LDL) has the highest concentration of cholesterol and is the biggest offender in Atherosclerosis.
    • High density lipoprotein (HDL) is the “good actor.” We’ll get into why in a moment or two.
    • Lipemia retinalis was shown in a patient that had serum triglycerides of 21,040mg/dL (normal is 10-190mg/dL). Instead of the normal red vessels they appear almost white.
    • Lipids can actually exit the vascular compartment and accumulate in the tissues, particularly the skin. They can be found around the eyes and throughout the skin resulting in xanthomas comprised of lipid engorged macrophages.
  • Hypertension
  • Cigarette smoking
  • Diabetes mellitus -- Although diabetes mellitus itself cannot be modified once you have it, there is some discussion about whether the risk of Atherosclerosis is lowered by maintaining tight control over blood glucose. Results at this point are unclear.
  • The four risk factors above are the “Big 4” that cause the vast majority of Atherosclerosis, but hyperhomocysteinemia and infection also can increase risk.
    • It is thought that causative agents of periodontitis may play a role in the pathogenesis of Atherosclerosis. This is a hotbed of debate and research in the dental world (so close, and yet so far away from us). And seeing as Dr. Cleveland is a dentist, I feel like a little tidbit like this might somehow find its way onto our exam…
    • Infection with Chlamydia pneumoniae seems to be the pathogen most closely associated with Atherosclerosis.
• Serum markers are increasingly important as predictors of coronary events like heart attacks.
  • These include elevated serum levels of C-reactive protein and plasminogen activator inhibitor I.
  • Both factors are associated with hemostasis, thrombosis, and inflammation.
• There are some uncertain risk factors
  • Obesity can lead to hypertension, diabetes, low HDL and hypertriglyceridemia.
  • Physical inactivity can also lead to a decrease in HDL.
  • Stressful life style (type A personality) may also play a role. Think of the stereotypical high-powered businessman that gets an MI at the age of 35. Good thing I'm not going into a stressful job!
• With multiple risk factors you don’t just double or triple your risk. The factors are synergistic.
  • Two risk factors means you have four times the risk of MI than someone with no factors.
  • Three risk factors means that you are seven times more likely to have an MI.

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