Atherosclerosis


What is atherosclerosis?

Atherosclerosis or arteriosclerosis refers to a buildup of plaques in the arteries and thus their hardening and narrowing.

Atherosclerosis word origin: from the Greek atheros = gruel – a soft, cooked cereal, which refers to a plaque + sclerosis = hardening [3]

Atherosclerosis

Arterial Plaque (Atheroma) Composition and Development

Arterial plaque is an abnormal deposition of fatty acids, cholesterol, calcium, inflammatory cells and connective tissue on the inner side of the large and medium-sized arteries [53]. Plaques can start to develop in childhood; most older people probably have some plaques but these obstruct the blood flow only when they occupy 50-70% of the artery diameter [2].

A plaque develops on the inner surface (intima) of the arteries that are damaged due to [2,53]:

  • Nicotine from tobacco smoke
  • High homocysteine levels (sometimes genetic or due to folate deficiency)
  • High angiotensin II levels (increased in high blood pressure)
  • Hyperglycemia > oxidative stress > free radicals > small oxidized LDL cholesterol particles
  • Systemic infection or inflammation
  • Turbulent blood flow

The above factors can inactivate nitric oxide, which normally dilates the arteries and decreases inflammation in them [53].

A plaque can be stable or unstable. An unstable plaque, even if it appears small on angiogram, can rupture and a blood clot (thrombus) can develop on the top of it and additionally obstruct the artery [53]. A part of the thrombus (embolus) can detach and lodge further in the artery where its diameter is smaller and completely blocks it, which can cause, for example, heart attack.

Causes and Risk Factors

The exact cause of atherosclerosis is not known but involves a damage and inflammation of the inner arterial layer (intima).

Main risk factors [2,5]:

  • Genetic factors (family history of premature coronary heart disease or stroke, familial hypercholesterolemia, male sex)
  • Older age
  • Cigarette smoking
  • High levels of total and LDL cholesterol and triglycerides and low levels of HDL cholesterol
  • High blood glucose levels (hyperglycemia in poorly controlled diabetes mellitus type 1 or type 2 [insulin resistance])
  • High blood pressure (hypertension)

Other possible risk factors [5,53]:

  • Metabolic syndrome (a combination of abdominal obesity, high blood pressure, high glucose and triglyceride levels and low HDL cholesterol levels); the main causes are probably lack of physical inactivity and insulin resistance
  • Excessive alcohol drinking (moderate alcohol drinking with <2 drinks/day for men and <1 drink/day for women does not increase the risk)
  • Lack of antioxidants (vitamin A, C, E, selenium, flavonoids) in the diet
  • High levels of small oxidized LDL particles, fibrinogen and lipoprotein(a), low levels of alphalipoprotein
  • Chronic inflammatory disease, such as systemic lupus erythematosus (SLE), rheumatoid arthritis or systemic sclerosis [1]
  • Chronic kidney disease
  • Infection with Chlamydophila pneumoniae, Helicobacter pylori or citomegalovirus (CMV)
  • Psychological stress, depression
  • Living near a busy road (long-term exposure to traffic-related dust and night-time traffic noise) [54]

Symptoms, Signs and Complications

Mild atherosclerosis may not cause any symptoms but severe atherosclerosis can result in [2]:

  • Narrowing of the coronary arteries (coronary heart disease) with chest pain (angina pectoris) triggered by exercise or stress; or, eventually, heart attack (myocardial infarct), which can be deadly
  • Narrowing of the carotid arteries in the neck or cerebral arteries in the brain, which can result in transient ischemic attack (TIA) or stroke (cerebral infarct) with a sudden loss of consciousness, muscle paralysis and loss of sensation on one side of the body or death
  • Narrowing of the arteries in the legs (peripheral artery disease or arteriosclerosis obliterans) withe pain, tingling and numbness triggered by walking (intermittent claudication)
  • Narrowing of the arteries in the pelvis with pelvic pain and erectile dysfunction
  • Renal artery stenosis, which can result in chronic kidney disease with nausea, increased urination and leg swelling
  • Narrowing and hardening of the abdominal aorta, which can cause abdominal pain (only in late stage)
  • Narrowing of the intestinal (mesenteric) arteries, which can cause pain after meals, black stools, diarrhea and weight loss

Atherosclerosis in early stages usually does not cause any signs. In developed atherosclerosis, a doctor can detect weak pulse in the posterior tibial artery behind the inner ankles, radial artery in the wrists or carotid artery in the neck, and, sometimes, bluish discoloration (cyanosis) of the lower legs and leg ulcers.

Atherosclerosis is more common in men than in women and it causes symptoms in mean earlier (typically after 45 years of age) than in women (usually after 55 years of age) [2]. Estrogen hormones seem to be somewhat protective against atherosclerosis, so this is why women often develop it after menopause, when the estrogen levels fall [53].

Diagnosis

Most people with atherosclerosis who have no symptoms are not aware of the condition. Sometimes, a doctor accidentally detects atherosclerosis during investigations for other conditions, such as chest ultrasound or computed tomography (CT) of the brain.

Atherosclerosis can be detected by the following investigations:

  • CT angiography as the initial investigation
  • Coronary angiography or cardiac catheterization (an X-ray image of the coronary arteries after injecting a contrast substance into them)
  • Electron-beam computed tomography (EBCT)
  • Nuclear perfusion imaging with single-photon emission computed tomography (SPECT)
  • Positron emission tomography (PET)
  • Carotid artery intima-media thickness (CIMT) measured by ultrasound
  • Intravascular ultrasound (IVUS)
  • Magnetic resonance imaging (MRI)

Treatment

Atherosclerosis cannot be cured but it can be treated.

Drugs

The following drugs can reduce the risk factors for atherosclerosis [2,53]:

  • To lower high LDL cholesterol: statins (atorvastatin, lovastatin, simvastatin) [4] and bile acid sequestrans (cholestyramine, colestipol)
  • To raise low HDL cholesterol: vitamin B3 or niacin (insufficient evidence of additional effectiveness when used with statins) [55,56], fibrates (fenofibrate)
  • To reduce blood clotting: aspirin [4] or clopidogrel
  • To lower high blood pressure: ACE inhibitors [57], beta-blockers [58]

Smoking cessation [61], weight loss (in overweight individuals with high blood pressure) [62] and aggressive treatment of high LDL cholesterol and blood pressure [59,60] can–at least partly–reverse atherosclerosis.

Surgery

  • In coronary heart disease: coronary artery angioplasty or coronary artery bypass grafting (CABG)
  • In atherosclerosis of the carotid artery: carotid endarterectomy (removal of a plaque from the artery)
  • In atherosclerotic ileal arteries or arteries in the lower legs: by pass surgery

Prevention

If you have a strong family history of coronary heart disease or stroke, you may be not able to completely prevent atherosclerosis but you may slow down its development.

Diet

Vegetarian [33,34,35] and Mediterranean diet (whole grains, fruits vegetables, olive oil, nuts, seeds, fish, wine) [36,37,38,39,40] have been associated with the lower risk of atherosclerosis than other diets.

There is SOME EVIDENCE that replacing some of saturated fats (processed meat, beef, pork and lamb) with polyunsaturated fats (fatty fish) in the diet can reduce the risk of coronary heart disease [63,64,65].

Regular consumption–at least twice weekly–of fatty fish (mackerel, salmon, sardines, halibut, trout), which are high in omega-3 polyunsaturated fatty acids EPA and DHA have been associated with lower risk of coronary artery disease [35,48,49]. However, there is INSUFFICIENT EVIDENCE that fish oil supplements would help to prevent coronary heart disease or atherosclerosis in general [28,29,30,48,49].

In some people with high blood pressure and high sodium intake, reducing sodium intake can lower blood pressure and thus decrease the risk of coronary heart disease [50,51].

High consumption of trans fat from foods like French fries, cheeseburgers, chicken nuggets, commercially baked biscuits, crackers, doughnuts and pies, hard margarines, vegetable shortening, other foods with added “partially hydrogenated oil” or Vanaspati ghee have been associated with increased risk of atherosclerosis [43,44,45,46,47].

High consumption of processed meat (bacon, bologna, corned beef, ham, hamburgers, hot dogs, deli or luncheon meats, salami and sausages), which contain preservatives, such as salt, nitrites, nitrates and nitrosamine, but not unprocessed red meat (beef, pork and lamb), has been associated (not necessary cause-effect related) with higher incidence of coronary heart disease [52].

Supplements and Herbs

There is INSUFFICIENT EVIDENCE about the preventative effect of the following supplements on atherosclerosis:

  • Minerals: calcium [20], chromium [28], iron [28], magnesium [19,28], potassium [21]selenium [28]
  • Vitamins: beta carotene [6], vitamin A, C [28] or E [6,13,28], which are all antioxidants, vitamin B6, B12 or folate [14,28], vitamin D or K [28], choline [15]
  • Phytonutrients: lycopene [28], flavanols in green or black tea [9] chocolate and cocoa [24,25,28], flavonoids, including resveratrol (fruits, vegetables, red wine) [10,28], soy isoflavones [12], phytosterols [17,18]
  • Herbs: Ayurvedic medicine (curcumin from turmeric [31,41], ginger [32], mukul myrrh tree [28]), Chinese herbal medicine (Danshen, ginkgo biloba, ginseng, horse chestnut, lingzhi, red yeast rice extract, rosemary extract, Tong-xin-luo [7]) [27,28], garlic [16,28]
  • Other: coenzyme Q10 [8,28], alpha-linolenic acid (flaxseed oil) [11], monounsaturated fatty acids from olive oil or nuts [22,23], L-carnitine [28]

Atherosclerosis Prevention and Reversal

To reverse or at least slow down the development of atherosclerosis, try [59,60,61,62]:

  1. Maintain healthy body weight.
  2. Maintain normal blood pressure.
  3. Maintain normal blood cholesterol, triglyceride and glucose levels.
  4. Eat what helps you achieve the above goals.
  5. Be physically active (aerobic exercise, such as walking or running seems to be most protective)
  6. Do not smoke.


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