**1. Introduction**

Atherosclerotic cardiovascular disease is a group of disease which contains coronary artery disease, carotid artery disease, upper and lower extremity disease, and renal arterial diseases. The main cause of atherosclerotic cardiovascular diseases is the atherothrombotic process that occurs with atherosclerotic plaque rupture. Atherosclerosis is a chronic lipid-associated inflammatory disease concomitant with intimal thickening, especially involving bifurcation regions where endothelial damage is particularly high. Hypertension, hyperlipidemia,

© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2018 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

diabetes, and smoking are the main risk factors for atherosclerosis. Fibrinogen, hsCRP, and interleukin-6 (IL-6) which are markers for inflammation have been found elevated in atherosclerosis. Atherosclerotic diseases are also common with systemic inflammatory diseases such as lupus and rheumatoid arthritis.

**4. Atherosclerosis and cholesterol hypothesis**

hyperlipidemia and atherosclerosis [2, 5, 6].

**5. LDL and total cholesterol**

small dense LDL.

The hypothesis of cholesterol suggests that lipids play a major role in the development of atherosclerosis. The 4S trial (Scandinavian Simvastanin Survival Study) showed that while there was significant reduction in total cholesterol level, LDL cholesterol level, and decrease in major coronary events, HDL cholesterol level was elevated in simvastatin receiving group [4]. After 4S study, REVERSAL, ASTEROID, and SATURN studies revealed that parallel plaque regression was observed with aggressive lipid-lowering therapy and reduction in major cardiovascular events was achieved. These similar studies have proven the relationship between

Role of Cholesterol as a Risk Factor in Cardiovascular Diseases

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Statins reduce macrophages and extracellular lipid accumulation in atherosclerotic plaque region and increase the content of collagen in the extracellular matrix which result in intimal calcification. Statins also stabilize inflammation and coagulation cascade after plaque rupture.

LDL is the particle that is responsible for transporting cholesterol to tissues. Cholesterol transportation is achieved by binding of the LDL receptor and apoB. There are three separate fractions of LDL: LDL (large/floating), IDL, and small dense LDL. The most atherogenic LDL is

In the WOSCOP trial and the AFCAPS/TeXCAPS trial which used pravastatin and lovastatin, respectively, the effect of hyperlipidemic therapy on the primary prevention of coronary artery disease was shown [7, 8]. The ASCOT-LLA study was terminated early in hypertensive individuals because atorvastatin significantly reduced nonfatal MI and CAD-induced mortality [9]. Similarly, the CARDS study was terminated early in diabetic individuals because

LIPID study compared low-dose and high-dose atorvastatin in patients with stable coronary artery disease and mortality was similar in both groups, but there was a significant decrease in major cardiovascular events in the high-dose atorvastatin group. The HPS study has shown that statin therapy protects high-risk patients with LDL cholesterol levels below 116 mg/dL [11]. CARE study with pravastatin in acute MI and MIRACLE study with atorvastatin in

In the ASTEROID trial, high-dose statin therapy (rosuvastatin 40 mg/day) was shown to reduce 53% LDL cholesterol, 15% increase in HDL cholesterol, and regression in 78% atheroma [5].

Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors inhibit the PCSK9 protein, which is effective in LDL receptor synthesis and provide 50–70% reduction in LDL-C levels.

In the ACCELERATE study, it was shown that the CETP inhibitor (Evacetrapib) did not

reduce major cardiovascular events despite a 39% reduction in cholesterol level [14].

atorvastatin decreased 37% in major cardiovascular events and 48% in stroke [10].

USAP or MI have shown early initiation of statins have a positive affect [12, 13].
