The Pathophysiology of Atherosclerotic Heart Disease.
The association of increased intake of saturated fats with
atherosclerosis has been long established from animal studies
originally, by the work of Ignatowski [42] in 1908 and subsequently
by the work of other investigators [43-45]. Atherosclerosis is the
most frequent underlying cause of CAD, and CVD and is the major cause of
CV mortality worldwide accounting for 17.3 million deaths/year, or
31.5% of the total death rate globally in 203 [46]. Saturated fat
is rich in LDL-C, which has been considered the culprit for the
pathogenesis of atherosclerosis [47], confirmed by genetic [48],
epidemiologic [49], and clinical studies [50]. Therefore, the
rationale for decreasing the intake of saturated fats is solid on
scientific grounds. Several studies have demonstrated that reducing the
saturated fat content of the diet and replacing it with polyunsaturated
fats has resulted in a decreased incidence of CVD [51,52]. Also,
populations with low intake of saturated fats, like those in the East
Asian and Mediterranean countries, as well as the consumption of other
diets low in saturated fats has been associated with a low incidence of
ASCVD [53-55]. Since the effect of LDL-C on the risk of future ASCVD
appears to be causal as well as cumulative over time, the earlier
lowering of LDL-C may result, proportionally, in greater long-term
reduction of ASCVD. It has been demonstrated that reduction of LDL-C by
1 mmol/L (38.7 mg/dl) will reduce the relative risk of future ASCVD by
about 10% the 1st year, 16% the
2nd year and 20% the 3rd year
[49]. Another factor regarding the atherogenic effects of LDL, is
its consistency and particle size. LDL is a spherical particle 22-29 nm
in diameter, with a core of esterified cholesterol and triglyceride, a
lipid coat of non-esterified cholesterol and phospholipid, and a
structural apoB protein, which is recognized by the LDL receptors that
remove LDL from the plasma [56]. This structure of LDL consists of
small dense sizes and of larger less dense sizes, and several studies
have suggested that the small dens size of LDL is more atherogenic
[57,58], because it is more prone to oxidation and has greater
affinity for the proteoglycans of the arterial wall facilitating its
entrance into the arterial wall [59]. Also, small size LDL is
present in high risk patients with increased triglyceride and low HDL
levels, diabetes, insulin resistance, obesity, and the metabolic
syndrome [60-62]. However, other observational studies have shown
that large size LDL is also, atherogenic and predicts a higher incidence
of CVD [63,64], although the preponderance of evidence supports the
atherogenic properties of small dense LDL. Perhaps this controversy may
not be important clinically, since both low size and large size LDLs
respond equally well to treatment with statins [64].