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of the
Framingham Heart Study in the early 1960s. The understanding of such factors is critical to the prevention of
cardiovascular morbidities and mortality. See the image below.
Older age: Over age 45 years in men and over age 55 years in women
Family history of early heart disease
Race: Among persons with CAD, the cardiovascular death rate for African Americans is reported to be
particularly high; in Asians, low levels of high-density lipoprotein cholesterol (HDL-C), which are considered to
be a risk factor for coronary heart disease, appear to be especially prevalent; South Asians appear to have a
higher independent risk for cardiovascular disease as well.
Modifiable risk factors
High levels of the following are considered to be risk factors for CAD:
C-reactive protein (CRP): High levels are related to the presence of inflammation and, according to
some research results, may be associated with an increased risk of CAD development and heart attack [2]
Lipoprotein(a)
Homocysteine: In the general population, mild to moderate elevations are due to insufficient dietary
intake of folic acid, but homocysteine levels may also identify people at increased risk for heart disease
Small, dense LDL-C particles
Fibrinogen
Various medical conditions that can contribute to CAD include the following:
Tissue plasminogen activator (tPA): An imbalance of the clot dissolving enzymes (eg, tPA) and their
respective inhibitors (plasminogen activator inhibitor-1 [PAI-1]) may predispose individuals to myocardial
infarctions
Low serum testosterone levels: Have a significant negative impact on patients with CAD
Hysterectomy: A study suggests that this becomes a risk factor later in life in women who have the
surgery at or before age 50 years
Lack of sleep
Electron-beam computed tomography (EBCT) scanning: To identify coronary calcification; can reveal
at-risk individuals and perhaps allow for medical monitoring [6]
64-slice CT angiography: Bulky plaques may be identified in asymptomatic patients; the risk-benefit of
using CT angiography in an asymptomatic patient for the identification of atherosclerotic plaques is still a
subject of much debate
Carotid intima-media thickness (IMT), pulse wave velocity (PWV), and the ankle-brachial index (ABI):
Widely used, noninvasive modalities for evaluating atherosclerosis
Biomarkers
In a 10-year comparison of 10 biomarkers for predicting death and major cardiovascular events in
approximately 3000 individuals, the most informative biomarkers for predicting death were as follows:
PATHO
including activation, proliferation, migration, and cell death, as well as new vessel
formation, geometric remodeling, healing, or destruction of extracellular matrix of
arteries and the myocardium.2 Certain constituents of the extracellular matrix (notably
proteoglycans) bind lipoproteins, prolong their residence in the intima, and render them
more susceptible to oxidative modification and glycation (nonenzymaticc conjugation
with sugars).3 These products of lipoprotein modification, including oxidized
phospholipids and advanced glycation end products, sustain and propagate the
inflammatory response.4,5 As the lesion progresses, calcification may then occur through
mechanisms similar to those in bone formation.6 In addition to proliferation, cell death
(including apoptosis) commonly occurs in the established atherosclerotic lesion. 7The
death of lipid-laden macrophages can lead to extracellular deposition of tissue factor
(TF), some in particulate form.8 The extracellular lipid that accumulates in the intima can
coalesce and form the classic, lipid-rich necrotic core of the atherosclerotic plaque.
Arterial Remodeling, a Clinically Critical Component of Atherogenesis
From a practical clinical perspective, few aspects of the biology of atherogenesis have
had more recent impact than the concept of arterial remodeling (Figure 1). Driven by
the ascendancy of angiography and the success of revascularization strategies that
target arterial stenoses, the degree of arterial narrowing dominated our thinking about
the pathophysiology of CAD for decades. We viewed the risk of events as dependent on
the degree of stenosis and envisioned atherosclerosis as a segmental or focal disease.
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Pathophysiology
Coronary artery disease is almost always due to atheromatous narrowing and
subsequent occlusion of the vessel. Early atheroma (from the Greek athera (porridge)
and oma (lump)) is present from young adulthood onwards. A mature plaque is
composed of two constituents, each associated with a particular cell population. The
lipid core is mainly released from necrotic foam cellsmonocyte derived
macrophages, which migrate into the intima and ingest lipids. The connective tissue
matrix is derived from smooth muscle cells, which migrate from the media into the
intima, where they proliferate and change their phenotype to form a fibrous capsule
around the lipid core.