Wikipedia begins, “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 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).
Atherosclerosis is a chronic disease that remains asymptomatic for decades. Atherosclerotic lesions, or plaques, cause narrowing 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, 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, “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.
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 a fatty nodule in the eroded 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. According to the theory, this triggers more white blood cells, continuing the cycle. 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 modifiable. The points labeled ‘+’ in the list below form the components of Metabolic Syndrome, first described in Retrospective #9 below and discussed in multiple columns.
Modifiable Risk Factors
· +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
· +Hypertension, on its own increasing risk by 60%
· Elevated serum C-Reactive Protein (hsCRP) concentrations
· 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 +, high homocysteine, uric acid, or fibrinogen or lipoprotein(a) concentrations, chronic systemic inflammation, as reflected by upper-normal WBC concentrations, elevated hs-CRP or serum insulin levels +, stress or symptoms of clinical depression, hyperthyroidism, short sleep duration and Chlamydia pneumoniae infection.