**5. LDL and total cholesterol**

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

Atherogenesis starts early in life. Subintimal lipoprotein accumulation and leukocyte adhesion occurs as a result of increased endothelial permeability due to endothelial damage. Intimal neovascularization is seen with the migration of vasa vasorum into the intima. There is a structure in the luminal side of the atherosclerotic plaque that is called fibrous cap which contains molecules such as smooth muscle, collagen, and elastin. External elastic lamina is placed adjacent to the atherosclerotic plaque and tunica media and the lipid core is found between these two structures and it is made from the cholesterol crystals, smooth muscle

Atherosclerotic plaques create luminal stenosis in the advanced stage. The first study in this subject was conducted by Glagov et al. in autopsy material of a patient with 136 left main coronary artery (LMCA) lesions. In this study, there is a positive correlation between internal elastic membrane area and plaque area, and luminal stenosis is prevented by expansion of the compensator at the atheromatous load of less than 40% [1]. In the REVERSAL trial, statin therapy was performed in patients with asymptomatic coronary artery disease. Atheroma volume, percentage of atheroma volume, and atheromatous change in the diseased segment were evaluated and progression of coronary atherosclerosis was observed in the pravastatin receiving group compared to baseline but no progression of atherosclerosis was observed in

The lipid core that carries triglycerides and cholesterol esters has a hydrophobic structure and is coated with polar capsules which contain apolipoproteins, phospholipids, and nonesterified cholesterol crystals. When the lipoproteins were classified according to their migration rates in lipoprotein electrophoresis, the band closest to the origin formed the chylomicron band; low-density lipoprotein (LDL) in the beta band, very-low-density lipoproteins (VLDL) in the pre-beta band, and high-density lipoprotein (HDL) in the alpha band, respectively.

Chylomicron is synthesized in liver from dietary fat molecules. Since chylomicrons and VLDL molecules larger than 70 nanometers cannot reach the subintimal region through the transcytotic transport system, chylomicrons do not have atherogenic potential. But chylomicron remnants are atherogenic and cannot be removed from circulation when they are present in high quantities [3]. Hydrolysis of the chylomicrons with lipoprotein lipase results in the formation of VLDL. The majority of VLDL is converted to LDL. Chylomicrons are attached to ApoB48. Chylomicron rem-

nants, LDL, and VLDL are connected to apoB100 and are called non-HDL cholesterol.

as lupus and rheumatoid arthritis.

96 Cholesterol - Good, Bad and the Heart

**2. Pathogenesis of atherosclerosis**

cells, vascular structures, and foam cells.

the atorvastatin group [2].

**3. Lipoprotein structure**

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 small dense LDL.

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

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

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].
