Sunday, April 15, 2012

The Nutrition Debate #48: Inflammation and Atherosclerosis

“Atherosclerosis…is a condition in which an artery wall thickens as a result of the accumulation of fatty materials such as cholesterol. It is a syndrome affecting arterial blood vessels, a chronic inflammatory response in the walls of arteries, caused largely by the accumulation of macrophage white blood cells and promoted by low-density lipoproteins (LDL) -- plasma proteins that carry cholesterol and triglycerides -- without adequate removal of fats and cholesterol from the macrophages by…high-density lipoproteins (HDL)” (all italics added).  So begins the Wikipedia entry on Atherosclerosis.
Atherosclerosis is a chronic disease that remains asymptomatic for decades. Atherosclerotic lesions, or plaques, cause narrowing (stenosis) of the artery and, if unstable, can rupture and induce a thrombus (blood clot, attached or motile). A thrombus, in place or more likely downstream, can cause an occlusion of the lumen of the artery, stopping blood flow (ischemia), resulting in the death of tissues fed by the artery. This catastrophic event is called infarction. Thrombosis in the coronary artery is a myocardial infarction (heart attack). Stroke is often caused by a clot in the carotid artery.
These complications of advanced atherosclerosis are chronic, slowly progressive and cumulative. What’s “new” in the understanding of atherosclerosis, however, is an appreciation of the role of inflammation in atherosclerosis. The 2002 abstract of a paper titled “Inflammation and Atherosclerosis” begins, “Atherosclerosis, formerly considered a bland lipid storage disease, actually involves an ongoing inflammatory response.” The full paper was published in Circulation (2002; 105:1135-1143), the Journal of the American Heart Association, under the banner “Clinical Cardiology: New Frontiers.”
The main cause of atherosclerosis is yet unknown, but a considerable body of experimental evidence points to oxidized LDL. This hypothesis posits that the inflammatory processes in the artery wall are initiated in response to retained low-density lipoprotein (LDL) molecules. The LDL molecule is globular shaped with a hollow core whose purpose is to carry cholesterol throughout the body. Once inside the vessel wall, LDL molecules become susceptible to oxidation by free radicals, and become toxic to the cells. The damage caused by the oxidized LDL molecules triggers a cascade of immune responses which over time can produce an atheroma, the characteristic nodule in the artery wall.
The body’s immune system responds to the damage to the artery wall by sending specialized white blood cells (macrophages and T-lymphocytes) to absorb the oxidized-LDL forming specialized foam cells. These white blood cells are not able to process the oxidized-LDL, and ultimately grow, then rupture, depositing a greater amount of oxidized cholesterol into the artery wall. This triggers more white blood cells, continuing the cycle, according to the theory. The primary documented driver of this process is therefore oxidized-LDL particles within the artery wall.
According to Wiki, various anatomic, physiological and behavioral risk factors for atherosclerosis are known. They can be divided into the categories modifiable or not. The points labeled ‘+’ in the list below form the core components of Metabolic Syndrome, discussed in multiple columns in The Nutrition Debate, starting with column #9.
·         Diabetes or Impaired glucose tolerance (IGT) +
·         Dyslipoproteinemia (unhealthy patterns of serum proteins carrying fats and cholesterol, such as) +
o   High LDL (bad if elevated and small/dense particles) and/or High VLDL
o   Low HDL (protective if large/fluffy particles and high enough)
o   An LDL:HDL ratio great than 3:1
·         Elevated serum C-Reactive Protein concentrations
·         Hypertension +, on its own increasing risk by 60%
·         Vitamin B6 deficiency
·         Tobacco smoking, increases risk by 200% after several pack years
·         Periodontal disease
Non-modifiable risk factors include advanced age, male sex, having close relatives who have some complication of atherosclerosis (e.g. coronary heart disease or stroke), and genetic abnormality, e.g. familial hypercholesterolemia.
Other lesser or uncertain risk factors for atherosclerosis includes obesity +, a sedentary lifestyle, hypercoagulability, post-menopausal estrogen deficiency, high intake of saturated fat (may raise total and LDL cholesterol), intake of trans fats (may raise total and LDL cholesterol while lowering HDL), high carbohydrate intake, elevated triglycerides +, homocysteine, uric acid, or fibrinogen or lipoprotein(a) concentrations, chronic systemic inflammation, as reflected by upper normal WBC concentrations, elevated hs C-reactive protein or serum insulin levels +, stress or symptoms of clinical depression, hyperthyroidism (over-active thyroid), short sleep duration and Chlamydia pneumoniae infection. That only leaves dietary causes of inflammation that cause atherosclerotic plaque, the subject of the next column.

© Dan Brown 4/15/12

1 comment:

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