the patient's ASCVD score, with patients with a 10-year ASCVD risk score >7.5% qualifying for moderate-intensity statin therapy, and for patient' with a 10-year ASCVD risk score >20% qualifying for moderate to high-intensity statin therapy. Beyond the 10-year ASCVD risk score, clinician-patient discussions of dyslipidemia and primary risk prevention should consider multiple factors, including patient preference, likelihood of statin side effects, prospective benefit of intensive lifestyle modifications, and presence or absence of risk-enhancing factors. Important riskenhancing factors to consider include metabolic syndrome, chronic kidney disease, chronic inflammatory or infectious conditions such as rheumatologic disease or HIV/AIDs, high-risk race or ethnicity, family history of premature ASCVD, and presence of lipid levels or biomarkers associated with increased ASCVD risk such as elevated Lp(a).

#### **Figure 5.**

*Management algorithm of dyslipidemia for secondary prevention of ASCVD (adapted from 2018 AHA/ACC/ ACCVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol).*

**27**

**7.1 Statins**

therapy [101, 172, 173].

lowering LDL-C by less than 30%.

combination therapy with statins [100].

**7.2 Nonstatins**

*Dyslipidemia and Its Role in the Pathogenesis of Atherosclerotic Cardiovascular Disease…*

drug that decreased small intestine absorption of cholesterol (**Figure 5**).

or non HDL-C > 100, the addition of PCSK9 inhibitors can be considered.

**7. Current and future therapy targets for dyslipidemia ASCVD**

volume, and diminish high-risk or vulnerable plaque features [174–176].

For patients with the aforementioned high-risk conditions who are on the maximal tolerated dose of statin therapy and ezetimibe with persistently elevated LDL-C > 70

Dyslipidemia therapy for the primary and secondary prevention of ASCVD, both current and therapies under investigation for future use, are centered on targeting LDL-C given the extensive evidence demonstrating the relationship between LDL and ASCVD, and no class of medications has been shown to be more effective at lowering LDL-C than statins, the foundation of lipid and cholesterol lowering

Statins inhibit HMG-CoA reductase, the rate-limiting enzyme in the synthetic pathway of cholesterol, resulting in lowering of tissue cholesterol, most critically intrahepatic cholesterol, and reflex increase in hepatic expression of surface LDLR and accompanying enhancement of receptor-mediated uptake of LDL and other circulating lipoproteins [172, 174]. Beyond the inhibition of hepatic cholesterol synthesis and the resulting reduction in circulating LDL, statins have demonstrated other important benefits in atherosclerotic plaque progression and the risk of acute atherothrombosis [174, 175]. Statins promote plaque stabilization by reducing inflammation and increasing collagen content in atherosclerotic plaques, slow the progression of overall plaque

Statin dosing intensity is categorized by expected reduction in LDL-C, with high-intensity statins typically lowering LDL-C by at least 50%, moderate-intensity statins typically lowering LDL-C by 30–49%, and low-intensity statins typically

There are different classes of non-statin medications used in the management of dyslipidemia, including bile acid sequestrants (cholestyramine, colestipol, and colesevelam), niacin, and fibrate, with ezetimibe and the PCSK9 inhibitors being the non-statin classes of medications that incorporated into the guidelines for dyslipidemia management in the primary and secondary prevention of ASCVD in

Management of dyslipidemia for the secondary prevention of ASCVD is centered on encouragement of intensive healthy lifestyle modifications and risk assessment for future ASCVD. Patients with high or very high-risk ASCVD are those with multiple major ASCVD events or one major ASCVD event and multiple high-risk conditions. Major ASCVD events include ACS within last 12 months, MI, ischemia CVA, PAD with claudication and ABI < 0.85, and PAD with previous revascularization or amputation. High-risk conditions are similar to the risk-enhancing factors that were considered for the management of dyslipidemia in the context of primary prevention of ASCVD, and include age > 65, history of CABG or PCI outside of the major ASCVD events, DM, hypertension, chronic kidney disease, current smoking status, congestive heart failure, and persistently elevated LDL-C above 100 mg/dL despite maximal tolerate dose of statin therapy and ezetimibe, an anticholesterol

*DOI: http://dx.doi.org/10.5772/intechopen.85772*

**6.3 Dyslipidemia: secondary prevention of ASCVD**

*Dyslipidemia and Its Role in the Pathogenesis of Atherosclerotic Cardiovascular Disease… DOI: http://dx.doi.org/10.5772/intechopen.85772*

#### **6.3 Dyslipidemia: secondary prevention of ASCVD**

Management of dyslipidemia for the secondary prevention of ASCVD is centered on encouragement of intensive healthy lifestyle modifications and risk assessment for future ASCVD. Patients with high or very high-risk ASCVD are those with multiple major ASCVD events or one major ASCVD event and multiple high-risk conditions. Major ASCVD events include ACS within last 12 months, MI, ischemia CVA, PAD with claudication and ABI < 0.85, and PAD with previous revascularization or amputation. High-risk conditions are similar to the risk-enhancing factors that were considered for the management of dyslipidemia in the context of primary prevention of ASCVD, and include age > 65, history of CABG or PCI outside of the major ASCVD events, DM, hypertension, chronic kidney disease, current smoking status, congestive heart failure, and persistently elevated LDL-C above 100 mg/dL despite maximal tolerate dose of statin therapy and ezetimibe, an anticholesterol drug that decreased small intestine absorption of cholesterol (**Figure 5**).

For patients with the aforementioned high-risk conditions who are on the maximal tolerated dose of statin therapy and ezetimibe with persistently elevated LDL-C > 70 or non HDL-C > 100, the addition of PCSK9 inhibitors can be considered.

### **7. Current and future therapy targets for dyslipidemia ASCVD**

#### **7.1 Statins**

*Dyslipidemia*

elevated Lp(a).

**26**

**Figure 5.**

*Cholesterol).*

*Management algorithm of dyslipidemia for secondary prevention of ASCVD (adapted from 2018 AHA/ACC/ ACCVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood*

the patient's ASCVD score, with patients with a 10-year ASCVD risk score >7.5% qualifying for moderate-intensity statin therapy, and for patient' with a 10-year ASCVD risk score >20% qualifying for moderate to high-intensity statin therapy. Beyond the 10-year ASCVD risk score, clinician-patient discussions of dyslipidemia and primary risk prevention should consider multiple factors, including patient preference, likelihood of statin side effects, prospective benefit of intensive lifestyle modifications, and presence or absence of risk-enhancing factors. Important riskenhancing factors to consider include metabolic syndrome, chronic kidney disease, chronic inflammatory or infectious conditions such as rheumatologic disease or HIV/AIDs, high-risk race or ethnicity, family history of premature ASCVD, and presence of lipid levels or biomarkers associated with increased ASCVD risk such as

> Dyslipidemia therapy for the primary and secondary prevention of ASCVD, both current and therapies under investigation for future use, are centered on targeting LDL-C given the extensive evidence demonstrating the relationship between LDL and ASCVD, and no class of medications has been shown to be more effective at lowering LDL-C than statins, the foundation of lipid and cholesterol lowering therapy [101, 172, 173].

> Statins inhibit HMG-CoA reductase, the rate-limiting enzyme in the synthetic pathway of cholesterol, resulting in lowering of tissue cholesterol, most critically intrahepatic cholesterol, and reflex increase in hepatic expression of surface LDLR and accompanying enhancement of receptor-mediated uptake of LDL and other circulating lipoproteins [172, 174]. Beyond the inhibition of hepatic cholesterol synthesis and the resulting reduction in circulating LDL, statins have demonstrated other important benefits in atherosclerotic plaque progression and the risk of acute atherothrombosis [174, 175]. Statins promote plaque stabilization by reducing inflammation and increasing collagen content in atherosclerotic plaques, slow the progression of overall plaque volume, and diminish high-risk or vulnerable plaque features [174–176].

> Statin dosing intensity is categorized by expected reduction in LDL-C, with high-intensity statins typically lowering LDL-C by at least 50%, moderate-intensity statins typically lowering LDL-C by 30–49%, and low-intensity statins typically lowering LDL-C by less than 30%.

#### **7.2 Nonstatins**

There are different classes of non-statin medications used in the management of dyslipidemia, including bile acid sequestrants (cholestyramine, colestipol, and colesevelam), niacin, and fibrate, with ezetimibe and the PCSK9 inhibitors being the non-statin classes of medications that incorporated into the guidelines for dyslipidemia management in the primary and secondary prevention of ASCVD in combination therapy with statins [100].

#### *Dyslipidemia*

Ezetimibe decreases small intestine cholesterol absorption by inhibiting the Niemann-Pick C1-Like 1 (NPC1L1) transporter [172, 177]. While the exact mechanisms of the effect of ezetimibe on atherosclerosis by itself are not as well defined as the effects of statins on atherosclerotic plaque progression and stabilization, the addition of ezetimibe to statins has been shown to regress plaque burden, reduce plaque volume, and promote plaque stabilization [178, 179]. PSCK9 works by interacting in with hepatic LDLR and enhancing the degradation of the receptor by hepatic lysosomes, with PSCK9 inhibitors thus mitigating the PSCK9-mediated turnover of hepatic LDLR and prolonging LDLR lifespan and uptake of circulating LDL-C [180]. PSCK9 inhibitors, namely alirocumab and evolocumab, in combination with statins have been shown to increase plaque calcification (a marker of plaque stability), and promote VSMC and collagen plaque content while simultaneously decreasing the size of the lipid necrotic core [181, 182].

### **7.3 New and future therapeutic targets and approaches to dyslipidemia and ASCVD**

Beyond the dramatic reductions in LDL-C and mechanisms of atherosclerotic plaque stabilization and slowing of progression effected by statins, ezetimibe, and PSCK9 inhibitors and their codification in the management algorithms for dyslipidemia and ASCVD: the other inflammatory, lipoprotein, and metabolic pathways involved in the pathophysiology of atherosclerosis serve as potential targets for therapies in the primary and secondary prevention of dyslipidemia and ASCVD.

The antiatherogenic properties of HDL, both in terms of its antioxidant and cholesterol efflux capacities, have led to investigations for the therapeutic potential of reconstituted HDL and methods to improve endogenous HDL functionality [23, 183]. Apo A-1 and apolipoprotein E (Apo E) are the atheroprotective apolipoprotein components of HDL, but studies involving Apo A-1/HDL mimetic peptides transcriptional upregulators of Apo A-1 did not result in significant regression of coronary atherosclerotic lesions despite the enhanced HDL-C efflux [184]. Apo E consists of three isoforms (Apo E2, Apo E3, and Apo E4) and promotes clearance of circulating TG-rich lipoprotein remnants, cholesterol efflux from macrophages preventing foam cell formation, and diminishes expression of adhesion molecules necessary for macrophage migration into the arterial intima [184–186]. ApoE exerts additional atheroprotective functions via tampering the inflammatory response by inhibiting T cells, lipoprotein oxidation, and resulting proliferation and migration of VSMCs, suppressing platelet aggregation, and restoring endothelial function by promoting release of NO [184, 187–190]. Given ApoE diverse protective properties at various stages of the atherosclerotic thromboinflammatory process, studies investigating the potential value of reconstituted HDL with favorable ApoE content or methods to promote increased ApoE profiles among endogenous HDL can serve substantial roles for the future management of dyslipidemia and ASCVD.

Given the extensive inflammatory pathways and processes underlying the pathogenesis of atherosclerosis, considerable work has been and is currently dedicated to anti-inflammatory targets of therapy in dyslipidemia and ASCVD, with drugs in various stages of research and development. The role of lipoprotein oxidation, most significantly LDL to ox-LDL, has prompted the study of therapeutic antioxidants in the management of dyslipidemia, and has shown promising benefits in secondary prevention of ASCVD after ACS within 12 months [191, 192]. The increase of ox-LDL levels due to phospholipase A2 activity which enzymatically generate phospholipids with atherogenic modifications has led to study of the role of phospholipase 2 inhibitors in the prevention of atherosclerosis [193]. Many other inflammatory pathway targets have been investigated for the management of dyslipidemia and ASCVD

**29**

USA

provided the original work is properly cited.

© 2019 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,

*Dyslipidemia and Its Role in the Pathogenesis of Atherosclerotic Cardiovascular Disease…*

including leukotriene pathway inhibitors (promote atherosclerotic plaque development and progression via chemoattraction of macrophages and other inflammatory cells and increasing endothelial permeability), chemokine CC motif ligand 2 (CCL2), also known as MCP1 (chemokine recruiter of plaque destabilizing macrophages), and blockade of potent inflammatory markers TNF and IL-1 [191, 194–196].

Atherosclerotic cardiovascular disease encompasses conditions carrying tremendous morbidity and mortality, and is the acute and chronic clinical manifestations of a progressive pathogenic process that is initiated by the inflammatory responses to dyslipidemia. The diverse metabolic and immune mechanisms at play in the thrombo-inflammatory pathophysiology of atherosclerosis are driven by disruptions in the body's native metabolism of cholesterol, triglycerides, and lipoproteins, with comorbid conditions and risk factors such as smoking, hypertension, and obesity promoting critical changes in cholesterol and lipoproteins that initiate a vicious cycle of lipoprotein accumulation, foam cell formation, and inflammatory reaction. The fact that so many immune cell lines and metabolic factors play important roles in the development of atherosclerosis serves as a pool of current and potential future targets for therapies in the primary and secondary prevention

and Amgad N. Makaryus3,4\*

*DOI: http://dx.doi.org/10.5772/intechopen.85772*

**8. Conclusion**

of dyslipidemia and ASCVD.

**Author details**

Perry Wengrofsky1

Hempstead, NY, USA

, Justin Lee2

Downstate Medical Center, Brooklyn, NY, USA

\*Address all correspondence to<EMAIL_ADDRESS>
1 Department of Internal Medicine, State University of New York,

2 Division of Cardiovascular Disease, Department of Medicine,

State University of New York, Downstate Medical Center, Brooklyn, NY, USA

4 Donald and Barbara Zucker School of Medicine at Hofstra/Northwell,

3 Department of Cardiology, Nassau University Medical Center, East Meadow, NY,

*Dyslipidemia and Its Role in the Pathogenesis of Atherosclerotic Cardiovascular Disease… DOI: http://dx.doi.org/10.5772/intechopen.85772*

including leukotriene pathway inhibitors (promote atherosclerotic plaque development and progression via chemoattraction of macrophages and other inflammatory cells and increasing endothelial permeability), chemokine CC motif ligand 2 (CCL2), also known as MCP1 (chemokine recruiter of plaque destabilizing macrophages), and blockade of potent inflammatory markers TNF and IL-1 [191, 194–196].

## **8. Conclusion**

*Dyslipidemia*

**ASCVD**

Ezetimibe decreases small intestine cholesterol absorption by inhibiting the Niemann-Pick C1-Like 1 (NPC1L1) transporter [172, 177]. While the exact mechanisms of the effect of ezetimibe on atherosclerosis by itself are not as well defined as the effects of statins on atherosclerotic plaque progression and stabilization, the addition of ezetimibe to statins has been shown to regress plaque burden, reduce plaque volume, and promote plaque stabilization [178, 179]. PSCK9 works by interacting in with hepatic LDLR and enhancing the degradation of the receptor by hepatic lysosomes, with PSCK9 inhibitors thus mitigating the PSCK9-mediated turnover of hepatic LDLR and prolonging LDLR lifespan and uptake of circulating LDL-C [180]. PSCK9 inhibitors, namely alirocumab and evolocumab, in combination with statins have been shown to increase plaque calcification (a marker of plaque stability), and promote VSMC and collagen plaque content while simultane-

**7.3 New and future therapeutic targets and approaches to dyslipidemia and**

Beyond the dramatic reductions in LDL-C and mechanisms of atherosclerotic plaque stabilization and slowing of progression effected by statins, ezetimibe, and PSCK9 inhibitors and their codification in the management algorithms for dyslipidemia and ASCVD: the other inflammatory, lipoprotein, and metabolic pathways involved in the pathophysiology of atherosclerosis serve as potential targets for therapies in the primary and secondary prevention of dyslipidemia and ASCVD. The antiatherogenic properties of HDL, both in terms of its antioxidant and cholesterol efflux capacities, have led to investigations for the therapeutic potential of reconstituted HDL and methods to improve endogenous HDL functionality [23, 183]. Apo A-1 and apolipoprotein E (Apo E) are the atheroprotective apolipoprotein components of HDL, but studies involving Apo A-1/HDL mimetic peptides transcriptional upregulators of Apo A-1 did not result in significant regression of coronary atherosclerotic lesions despite the enhanced HDL-C efflux [184]. Apo E consists of three isoforms (Apo E2, Apo E3, and Apo E4) and promotes clearance of circulating TG-rich lipoprotein remnants, cholesterol efflux from macrophages preventing foam cell formation, and diminishes expression of adhesion molecules necessary for macrophage migration into the arterial intima [184–186]. ApoE exerts additional atheroprotective functions via tampering the inflammatory response by inhibiting T cells, lipoprotein oxidation, and resulting proliferation and migration of VSMCs, suppressing platelet aggregation, and restoring endothelial function by promoting release of NO [184, 187–190]. Given ApoE diverse protective properties at various stages of the atherosclerotic thromboinflammatory process, studies investigating the potential value of reconstituted HDL with favorable ApoE content or methods to promote increased ApoE profiles among endogenous HDL can serve substantial roles for the future management of dyslipid-

Given the extensive inflammatory pathways and processes underlying the pathogenesis of atherosclerosis, considerable work has been and is currently dedicated to anti-inflammatory targets of therapy in dyslipidemia and ASCVD, with drugs in various stages of research and development. The role of lipoprotein oxidation, most significantly LDL to ox-LDL, has prompted the study of therapeutic antioxidants in the management of dyslipidemia, and has shown promising benefits in secondary prevention of ASCVD after ACS within 12 months [191, 192]. The increase of ox-LDL levels due to phospholipase A2 activity which enzymatically generate phospholipids with atherogenic modifications has led to study of the role of phospholipase 2 inhibitors in the prevention of atherosclerosis [193]. Many other inflammatory pathway targets have been investigated for the management of dyslipidemia and ASCVD

ously decreasing the size of the lipid necrotic core [181, 182].

**28**

emia and ASCVD.

Atherosclerotic cardiovascular disease encompasses conditions carrying tremendous morbidity and mortality, and is the acute and chronic clinical manifestations of a progressive pathogenic process that is initiated by the inflammatory responses to dyslipidemia. The diverse metabolic and immune mechanisms at play in the thrombo-inflammatory pathophysiology of atherosclerosis are driven by disruptions in the body's native metabolism of cholesterol, triglycerides, and lipoproteins, with comorbid conditions and risk factors such as smoking, hypertension, and obesity promoting critical changes in cholesterol and lipoproteins that initiate a vicious cycle of lipoprotein accumulation, foam cell formation, and inflammatory reaction. The fact that so many immune cell lines and metabolic factors play important roles in the development of atherosclerosis serves as a pool of current and potential future targets for therapies in the primary and secondary prevention of dyslipidemia and ASCVD.

## **Author details**

Perry Wengrofsky1 , Justin Lee2 and Amgad N. Makaryus3,4\*

1 Department of Internal Medicine, State University of New York, Downstate Medical Center, Brooklyn, NY, USA

2 Division of Cardiovascular Disease, Department of Medicine, State University of New York, Downstate Medical Center, Brooklyn, NY, USA

3 Department of Cardiology, Nassau University Medical Center, East Meadow, NY, USA

4 Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, USA

\*Address all correspondence to<EMAIL_ADDRESS>
© 2019 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.

## **References**

[1] Wu MY, Li CK, Hou MF, Chu PY. New insights into the role of inflammation in the pathogenesis of atherosclerosis. International Journal of Molecular Sciences. 2017;**18**(10): 2034, 1-18

[2] Rafieian-Kopaei M, Setorki M, Doudi M, Baradaran A, Nasri H. Atherosclerosis: Process, indicators, risk factors and new hopes. International Journal of Preventive Medicine. 2014;**5**(8):927-946

[3] Rader DJ, Pure E. Lipoproteins, macrophage function, and atherosclerosis: Beyond the foam cell. Cell Metabolism. 2005;**1**(4):223-230

[4] Helkin A, Stein JS, Lin S, et al. Dyslipidemia. Part I—Review of lipid metabolism and vascular cell physiology. Vascular and Endovascular Surgery. 2016;**50**(2):107-118

[5] Ference BA, Ginsberg HN, Graham I, et al. Low-density lipoproteins cause atherosclerotic cardiovascular disease. 1. Evidence from genetic, epidemiologic, and clinical studies. A consensus statement from the european atherosclerosis society consensus panel. European Heart Journal. 2017;**38**:2459-2472

[6] Feingold KR, Grunfeld C. Introduction to lipids and lipoproteins. In: De Groot LJ, Chrousos G, Dungan K, et al., editors. Endotext [Internet]. South Darmouth (MA): MDText.com, Inc.; 2000. Available from: https://www. ncbi.nlm.nih.gov/books/NBK305896/ [Accessed: Feb 2, 2018]

[7] Chan DC, Watts GF. Apolipoproteins as markers and managers of coronary risk. Q JM: An International Journal of Medicine. 2006;**99**(5):277-287

[8] Laler PR, Akinkuolie AO, Chu AY, et al. Atherogenic lipoprotein determinants of cardiovascular

disease and residual risk among individuals with low low-density lipoprotein cholesterol. Journal of the American Heart Association. 2017;**6**(7): e005549, 1-17

[9] Navab M, Reddy ST, Van Lenten BJ, Fogelman AM. HDL and cardiovascular disease: Atherogenic and atheroprotective mechanisms. Nature. 2011;**8**:222-232

[10] Tomkin GH, Owens D. The chylomicron: Relationship to atherosclerosis. International Journal of Vascular Medicine. 2012;**2012**:784536

[11] Wilhelm MG, Cooper AD. Induction of atherosclerosis by human chylomicron remnants. Journal of Atherosclerosis and Thrombosis. 2003;**10**(3):132-139

[12] Nakajima K, Nagamine T, Fujita MQ, et al. Apolipoprotein B-48: A unique marker of chylomicron metabolism. Advances in Clinical Chemistry. 2014;**64**:117-177

[13] Kei AA, Filippatos TD, Tsimihodimos V, Elisaf MS. A review of the role of apolioprotein C-II in lipoprotein metabolism and cardiovascular disease. Metabolism. 2012;**61**(7):906-921

[14] Olofsson SO, Boren J. Apolipoprotein B: A clinically important apolipoprotein which assembles atherogenic lipoproteins and prompts the development of atherosclerosis. Journal of Internal Medicine. 2005;**258**:395-410

[15] Nordestgaard BG, Tybjaerg-Hansen A. IDL, VLDL, chylomicrons and atherosclerosis. European Journal of Epidemiology. 1992;**8**(Suppl 1):92-98

[16] Carmena R, Duriez P, Fruchart JC. Atherogenic lipoprotein particles

**31**

*Dyslipidemia and Its Role in the Pathogenesis of Atherosclerotic Cardiovascular Disease…*

lipoprotein. Current Atherosclerosis

[26] Nielsen LB. Atherogenecity of lipoprotein(a) and oxidized low density lipoprotein: Insight from in vivo studeis of arterial wall influx. Degradation and Efflux. Atheroscler. 1999;**143**:229-243

[27] Feric NT, Boffa MB, Johnston SM, Koschinsky ML. Apolipoprotein(a) inhibits the conversion of Gluplasminogen to Lys-plasminogen: A novel mechanism for lipoprotein(a) mediated inhibition of plasminogen activation. Journal of Thrombosis and Haemostasis. 2008;**6**:2113-2120

[28] Gimbrone MA Jr, Garcia-Cardena G. Endothelial cell

2016;**118**(4):620-636

dysfunction and the pathobiology of atherosclerosis. Circulation Research.

[29] Forstermann U, Xia N, Li H. Roles of vascular oxidative stress and nitric oxide in the pathogenesis of atherosclerosis. Circulation Research. 2017;**120**:713-735

[30] Pernow J, Shemyakin A, Bohm F. New perspectives on endothelin-1 in atherosclerosis and diabetes mellitus. Life Sciences. 2012;**91**(13-14):507-516

[31] Li YS, Haga JH, Chien S. Molecular basis of the effects of shear stress on vascular endothelial cells. Journal of Biomechanics. 2005;**38**(10):1949-1971

[32] Tabas I, Garcia-Cardena G, Owens GK. Recent insights into the cellular biology of atherosclerosis. Journal of Cell Biology. 2015;**209**(1):13-22

[33] Mitra R, O'Neil GL, Harding IC, et al. Glycocalyx in atherosclerosisrelevant endothelium function as a therapeutic target. Current

Atherosclerosis Reports. 2017;**19**(12):63

[34] Linton MF, Yancey PG, Davies SS, et al. The role of lipids and lipoproteins in atherosclerosis. In: De Groot LJ,

Reports. 2005;**7**:389-395

*DOI: http://dx.doi.org/10.5772/intechopen.85772*

in atherosclerosis. Circulation. 2004;**109**(Suppl III):III-2-III-7

[17] Ivanova EA, Myasoedova VA, Melnichenko AA, et al. Small dense low-density lipoprotein as biomarker for atherosclerotic diseases. Oxidative Medicine and Cellular Longevity.

[18] Goldstein JL, Brown MS. The LDL receptor. Arteriosclerosis, Thrombosis, and Vascular Biology.

[19] Horton JD, Cohen JC, Hobbs HH. Molecular biology of PCSK9: Its role in LDL metabolism. Trends in Biochemical

2017;**2017**:1273042

2009;**29**(4):431-438

Sciences. 2007;**32**(2):71-77

2008;**118**:S\_1080-S\_1081

2012;**14**:101-107

Nature. 2016;**13**:48-60

2010;**31**:2844-2853

[20] Suma V, Sanyal S, Thakur A, Makaryus A, Hecht H. Abstract 1185: Changes in small dense LDL particle distrbution with addition of niacin to a statin regimen. Do the lipid sub-fractions change to a less atherogenic pattern? Circulation.

[21] Bandeali S, Farmer J. High-density lipoprotein and atherosclerosis: The role of antioxidant activity. Current Atherosclerosis Reports.

[22] Rye KA, Barter PJ. Cardioprotective functions of HDLs. Journal of Lipid Research. 2014;**55**(2):168-179

[23] Rosenson RS, Brewer BB Jr, Ansell BJ, et al. Dysfunctional HDL and atherosclerotic cardiovascular disease.

[24] Nordestgaard BG, Chapman MJ, Ray K, et al. Lipoprotein(a) as a cardiovascular risk factor: Current status. European Heart Journal.

[25] Koschinsky ML. Lipoprotein(a) and atherosclerosis. New perspectives on the mechanism of action of an enigmatic

*Dyslipidemia and Its Role in the Pathogenesis of Atherosclerotic Cardiovascular Disease… DOI: http://dx.doi.org/10.5772/intechopen.85772*

in atherosclerosis. Circulation. 2004;**109**(Suppl III):III-2-III-7

[17] Ivanova EA, Myasoedova VA, Melnichenko AA, et al. Small dense low-density lipoprotein as biomarker for atherosclerotic diseases. Oxidative Medicine and Cellular Longevity. 2017;**2017**:1273042

[18] Goldstein JL, Brown MS. The LDL receptor. Arteriosclerosis, Thrombosis, and Vascular Biology. 2009;**29**(4):431-438

[19] Horton JD, Cohen JC, Hobbs HH. Molecular biology of PCSK9: Its role in LDL metabolism. Trends in Biochemical Sciences. 2007;**32**(2):71-77

[20] Suma V, Sanyal S, Thakur A, Makaryus A, Hecht H. Abstract 1185: Changes in small dense LDL particle distrbution with addition of niacin to a statin regimen. Do the lipid sub-fractions change to a less atherogenic pattern? Circulation. 2008;**118**:S\_1080-S\_1081

[21] Bandeali S, Farmer J. High-density lipoprotein and atherosclerosis: The role of antioxidant activity. Current Atherosclerosis Reports. 2012;**14**:101-107

[22] Rye KA, Barter PJ. Cardioprotective functions of HDLs. Journal of Lipid Research. 2014;**55**(2):168-179

[23] Rosenson RS, Brewer BB Jr, Ansell BJ, et al. Dysfunctional HDL and atherosclerotic cardiovascular disease. Nature. 2016;**13**:48-60

[24] Nordestgaard BG, Chapman MJ, Ray K, et al. Lipoprotein(a) as a cardiovascular risk factor: Current status. European Heart Journal. 2010;**31**:2844-2853

[25] Koschinsky ML. Lipoprotein(a) and atherosclerosis. New perspectives on the mechanism of action of an enigmatic

lipoprotein. Current Atherosclerosis Reports. 2005;**7**:389-395

[26] Nielsen LB. Atherogenecity of lipoprotein(a) and oxidized low density lipoprotein: Insight from in vivo studeis of arterial wall influx. Degradation and Efflux. Atheroscler. 1999;**143**:229-243

[27] Feric NT, Boffa MB, Johnston SM, Koschinsky ML. Apolipoprotein(a) inhibits the conversion of Gluplasminogen to Lys-plasminogen: A novel mechanism for lipoprotein(a) mediated inhibition of plasminogen activation. Journal of Thrombosis and Haemostasis. 2008;**6**:2113-2120

[28] Gimbrone MA Jr, Garcia-Cardena G. Endothelial cell dysfunction and the pathobiology of atherosclerosis. Circulation Research. 2016;**118**(4):620-636

[29] Forstermann U, Xia N, Li H. Roles of vascular oxidative stress and nitric oxide in the pathogenesis of atherosclerosis. Circulation Research. 2017;**120**:713-735

[30] Pernow J, Shemyakin A, Bohm F. New perspectives on endothelin-1 in atherosclerosis and diabetes mellitus. Life Sciences. 2012;**91**(13-14):507-516

[31] Li YS, Haga JH, Chien S. Molecular basis of the effects of shear stress on vascular endothelial cells. Journal of Biomechanics. 2005;**38**(10):1949-1971

[32] Tabas I, Garcia-Cardena G, Owens GK. Recent insights into the cellular biology of atherosclerosis. Journal of Cell Biology. 2015;**209**(1):13-22

[33] Mitra R, O'Neil GL, Harding IC, et al. Glycocalyx in atherosclerosisrelevant endothelium function as a therapeutic target. Current Atherosclerosis Reports. 2017;**19**(12):63

[34] Linton MF, Yancey PG, Davies SS, et al. The role of lipids and lipoproteins in atherosclerosis. In: De Groot LJ,

**30**

*Dyslipidemia*

**References**

2014;**5**(8):927-946

[1] Wu MY, Li CK, Hou MF, Chu PY. New insights into the role of inflammation in the pathogenesis of atherosclerosis. International Journal of Molecular Sciences. 2017;**18**(10): 2034, 1-18

disease and residual risk among individuals with low low-density lipoprotein cholesterol. Journal of the American Heart Association.

[9] Navab M, Reddy ST, Van Lenten BJ, Fogelman AM. HDL and cardiovascular

atheroprotective mechanisms. Nature.

atherosclerosis. International Journal of Vascular Medicine. 2012;**2012**:784536

[11] Wilhelm MG, Cooper AD. Induction

[12] Nakajima K, Nagamine T, Fujita MQ, et al. Apolipoprotein B-48: A unique marker of chylomicron metabolism. Advances in Clinical Chemistry. 2014;**64**:117-177

[10] Tomkin GH, Owens D. The chylomicron: Relationship to

of atherosclerosis by human chylomicron remnants. Journal of Atherosclerosis and Thrombosis.

[13] Kei AA, Filippatos TD, Tsimihodimos V, Elisaf MS. A review of the role of apolioprotein C-II in lipoprotein metabolism and cardiovascular disease. Metabolism.

2012;**61**(7):906-921

2005;**258**:395-410

[14] Olofsson SO, Boren J.

apolipoprotein which assembles atherogenic lipoproteins and prompts the development of atherosclerosis. Journal of Internal Medicine.

Apolipoprotein B: A clinically important

[15] Nordestgaard BG, Tybjaerg-Hansen A. IDL, VLDL, chylomicrons and atherosclerosis. European Journal of Epidemiology. 1992;**8**(Suppl 1):92-98

[16] Carmena R, Duriez P, Fruchart JC. Atherogenic lipoprotein particles

2003;**10**(3):132-139

2017;**6**(7): e005549, 1-17

disease: Atherogenic and

2011;**8**:222-232

[2] Rafieian-Kopaei M, Setorki M, Doudi M, Baradaran A, Nasri H.

[3] Rader DJ, Pure E. Lipoproteins,

[4] Helkin A, Stein JS, Lin S, et al. Dyslipidemia. Part I—Review of lipid metabolism and vascular cell physiology. Vascular and Endovascular

atherosclerosis: Beyond the foam cell. Cell Metabolism. 2005;**1**(4):223-230

[5] Ference BA, Ginsberg HN, Graham I, et al. Low-density lipoproteins cause atherosclerotic cardiovascular disease. 1. Evidence from genetic, epidemiologic, and clinical studies. A consensus statement from the european atherosclerosis society consensus panel. European Heart Journal.

macrophage function, and

Surgery. 2016;**50**(2):107-118

2017;**38**:2459-2472

[6] Feingold KR, Grunfeld C.

[Accessed: Feb 2, 2018]

Medicine. 2006;**99**(5):277-287

[8] Laler PR, Akinkuolie AO, Chu AY, et al. Atherogenic lipoprotein determinants of cardiovascular

Introduction to lipids and lipoproteins. In: De Groot LJ, Chrousos G, Dungan K, et al., editors. Endotext [Internet]. South Darmouth (MA): MDText.com, Inc.; 2000. Available from: https://www. ncbi.nlm.nih.gov/books/NBK305896/

[7] Chan DC, Watts GF. Apolipoproteins as markers and managers of coronary risk. Q JM: An International Journal of

Atherosclerosis: Process, indicators, risk factors and new hopes. International Journal of Preventive Medicine.

Chrousos G, Dungan K, et al., editors. WEndotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000. Available from: https://www. ncbi.nlm.nih.gov/books/NBK343489/ [Accessed: Dec 24, 2015]

[35] Tabas I, Williams KJ, Boren J. Subendothelial lipoprotein retention as the initiating process in atherosclerosis. Update and therapeutic implications. Circulation. 2007;**116**(16):1832-1844

[36] Milstone DS, Ilyama M, Chen M, et al. Differential role of an NF- κB transcriptional response element in endothelial versus intimal cell VCAM-1 expression. Circulation Research. 2015;**117**:166-177

[37] Ramji DP, Davies TS. Cytokines in atherosclerosis: Key players in all stages of disease and promising therapeutic targets. Cytokine & Growth Factor Reviews. 2015;**26**(6):673-685

[38] Boullier A, Bird DA, Chang MK, et al. Scavenger receptors, oxidized LDL, and atherosclerosis. Annals of the New York Academy of Sciences. 2001;**947**:214-222

[39] Gistera A, Hansson GK. The immunology of atherosclerosis. Nature. 2017;**13**:368-380

[40] Miller YI, Choi SH, Fang L, Tsimikas S. Lipoprotein modification and macrophage uptake: Role of pathologic cholesterol transport in atherogenesis. Sub-Cellular Biochemistry. 2010;**51**:229-251

[41] Bleda S, de Haro K, Varela C, et al. Elevated levels of triglycerides and VLDL-cholesterol provoke activation of NLRP1 inflammasone in endothelial cells. International Journal of Cardiology. 2016;**220**:52-55

[42] Vaughan DE. PAI-1 and atherothrombosis. Journal of Thrombosis and Haemostasis. 2005;**3**:1879-1883

[43] Riches K, Porter KE. Lipoprotein(a): Cellular effects and molecular mechanisms. Cholesterol. 2012;**2012**:923289

[44] Lara-Guzman OJ, Gil-Izquierdo A, Medina S, et al. Oxidized LDL triggers changes in oxidative stress and inflammatory biomarkers in human macrophages. Redox Biology. 2018;**15**:1-11

[45] Zernecke A. Dendritic cells in atherosclerosis: Evidence in mice and humans. Arteriosclerosis, Thrombosis, and Vascular Biology. 2015;**35**:763-770

[46] Gronberg C, Nilsson J, Wigren M. Recent advances on CD4+ T cells in atherosclerosis and its implications for therapy. European Journal of Pharmacology. 2017;**816**:58-66

[47] van Duijn J, Kuiper J, Slutter B. The many faces of CD8+ T cells in atherosclerosis. Current Opinion in Lipidology. 2018;**28**(5):411-416

[48] Tabas I, Lichtman AH. Monocyte-macrophages and T cells in atherosclerosis. Immunity. 2017;**74**(4):621-634

[49] Decano JL, Aikawa M. Dynamic macrophages: Understanding mechanisms of activation as guide to therapy for atherosclerotic vascular disease. Frontiers in Cardiovascular Medicine. 2018;**5**:97

[50] Tabas I. Macrophage death and defective inflammation resolution in atherosclerosis. Nature Reviews Immunology. 2010;**10**:36-46

[51] Subramanian M, Tabas I. Dendritic cells in atherosclerosis. Seminars in Immunopathology. 2014;**36**(1):93-102

[52] Bennet MR, Sinha S, Owens GK. Vascular smooth muscle cells in

**33**

*Dyslipidemia and Its Role in the Pathogenesis of Atherosclerotic Cardiovascular Disease…*

British Journal of Pharmacology.

[62] Barter PJ, Nicholls S, Rye KA, et al. Antiinflammatory properties of HDL. Circulation Research.

[63] Ganjali S, Gotto AM Jr, Ruscica M,

[64] van der Stoep M, Korporaai SJ, Van Eck M. High-density lipoprotein as a modulator of platelet and coagulation responses. Cardiovascular Research.

[65] Phillips MC. Molecular mechanisms of cellular cholesterol efflux. The Journal of Biological Chemistry. 2014;**289**(35):24020-24029

[66] Yancey PG, Bortnick AE, Kellner-Weibel G, et al. Importance of different pathways of cellular cholesterol efflux. Arteriosclerosis, Thrombosis, and Vascular Biology.

[67] Lee MK, Moore XL, Fu Y, et al. High-density lipoprotein inhibits human M1 macorphage polarization through redistribution of caveolin-1. British Journal of Pharmacology.

[68] Sanson M, Distel E, Fisher EA. HDL

[69] Terasaka N, Wang N, Yvan-Charvet L, Tall AR. High-density lipoprotein protects macrophages from oxidized low-density lipoprotein-induced apoptosis by promoting efflux of 7-ketocholesterol via ABCG1. Proceedings of the National Academy

induces the expression of the M2 macrophage markers arginase 1 and fizz-1 in a STAT6-depedent process.

PLoS One. 2013;**8**(8):e74676

2013;**169**(3):493-511

2004;**95**:764-772

et al. Monocyte-to-HDLcholesterol ratio as a prognostic marker in cardiovascular disease. Journal of Cellular Physiology. 2018;**233**(12):9237-9246

2014;**103**(3):362-371

2003;**23**(5):712-719

2016;**173**(4):741-751

*DOI: http://dx.doi.org/10.5772/intechopen.85772*

atherosclerosis. Circulation Research.

[53] Wang J, Uryga AK, Reinhold J, et al. Vascular smooth muscle cell senescence promotes atherosclerosis and features of plaque vulnerability. Atherosclerosis.

[54] Gomez D, Owens GK. Smooth muscle cell phenotypic switching in atherosclerosis. Cardiovascular Research. 2012;**95**(2):156-164

[55] Ponticos M, Smith BD. Extracellular matrix synthesis in vascular disease. hypertension, and atherosclerosis. Journal of Biomedical Research.

2016;**118**(4):692-702

2015;**132**(20):1909-1919

2014;**28**(1):25-39

[56] Toma I, McCaffrey TA.

Reviews. 2006;**86**:515-581

2017;**8**:66-77

2018;**12**(3):275-268

Transforming growth factor-β and atherosclerosis: Interwoven atherogenic and atheroprotective aspects. Cell and Tissue Research. 2012;**347**(1):155-175

[57] Tedgui A, Mallat Z. Cytokines in atherosclerosis: Pathogenic and regulatory pathways. Physiological

[58] Brites F, Martin M, Guillas I, Kontush A. Antioxidative activity of high-density lipoprotein (HDL): Mechanistic insights into potential clinical benefit. BBA Clinical.

[59] Singh K, Singh R, Chandra S, Tyagi S. Paraoxonase-1 is a better indicator than HDL of atherosclerosis—A pilot study in North Indian population. Diabetes and Metabolic Syndrome: Clinical Research and Reviews.

[60] Peng ZY, Zhao SP, He BM, et al. Protective effect of HDL on endothelial NO production: The role of DDAH/ ADMA pathway. Molecular and Cellular Biochemistry. 2011;**351**(1-2):243-249

[61] Tran-Dinh A, Diallo D, Delbosc S, et al. HDL and endothelial protection. *Dyslipidemia and Its Role in the Pathogenesis of Atherosclerotic Cardiovascular Disease… DOI: http://dx.doi.org/10.5772/intechopen.85772*

atherosclerosis. Circulation Research. 2016;**118**(4):692-702

*Dyslipidemia*

Chrousos G, Dungan K, et al., editors. WEndotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000. Available from: https://www. ncbi.nlm.nih.gov/books/NBK343489/ Thrombosis and Haemostasis.

Cellular effects and molecular mechanisms. Cholesterol.

Medina S, et al. Oxidized LDL triggers changes in oxidative stress and inflammatory biomarkers in human macrophages. Redox Biology.

[45] Zernecke A. Dendritic cells in atherosclerosis: Evidence in mice and humans. Arteriosclerosis, Thrombosis, and Vascular Biology. 2015;**35**:763-770

[46] Gronberg C, Nilsson J, Wigren M. Recent advances on CD4+ T cells in atherosclerosis and its implications for therapy. European Journal of Pharmacology. 2017;**816**:58-66

[47] van Duijn J, Kuiper J, Slutter B. The many faces of CD8+ T cells in atherosclerosis. Current Opinion in Lipidology. 2018;**28**(5):411-416

[49] Decano JL, Aikawa M. Dynamic macrophages: Understanding mechanisms of activation as guide to therapy for atherosclerotic vascular disease. Frontiers in Cardiovascular

[50] Tabas I. Macrophage death and defective inflammation resolution in atherosclerosis. Nature Reviews Immunology. 2010;**10**:36-46

[51] Subramanian M, Tabas I. Dendritic cells in atherosclerosis. Seminars in Immunopathology. 2014;**36**(1):93-102

[52] Bennet MR, Sinha S, Owens GK. Vascular smooth muscle cells in

[48] Tabas I, Lichtman AH. Monocyte-macrophages and T cells in atherosclerosis. Immunity.

2017;**74**(4):621-634

Medicine. 2018;**5**:97

[43] Riches K, Porter KE. Lipoprotein(a):

[44] Lara-Guzman OJ, Gil-Izquierdo A,

2005;**3**:1879-1883

2012;**2012**:923289

2018;**15**:1-11

[35] Tabas I, Williams KJ, Boren J. Subendothelial lipoprotein retention as the initiating process in atherosclerosis. Update and

therapeutic implications. Circulation.

[36] Milstone DS, Ilyama M, Chen M, et al. Differential role of an NF- κB transcriptional response element in endothelial versus intimal cell VCAM-1 expression. Circulation Research.

[37] Ramji DP, Davies TS. Cytokines in atherosclerosis: Key players in all stages of disease and promising therapeutic targets. Cytokine & Growth Factor Reviews. 2015;**26**(6):673-685

[38] Boullier A, Bird DA, Chang MK, et al. Scavenger receptors, oxidized LDL, and atherosclerosis. Annals of the New York Academy of Sciences.

[39] Gistera A, Hansson GK. The immunology of atherosclerosis. Nature.

[40] Miller YI, Choi SH, Fang L, Tsimikas S. Lipoprotein modification and macrophage uptake: Role of pathologic cholesterol transport in atherogenesis. Sub-Cellular Biochemistry. 2010;**51**:229-251

[41] Bleda S, de Haro K, Varela C, et al. Elevated levels of triglycerides and VLDL-cholesterol provoke activation of NLRP1 inflammasone in endothelial

cells. International Journal of Cardiology. 2016;**220**:52-55

[42] Vaughan DE. PAI-1 and atherothrombosis. Journal of

[Accessed: Dec 24, 2015]

2007;**116**(16):1832-1844

2015;**117**:166-177

2001;**947**:214-222

2017;**13**:368-380

**32**

[53] Wang J, Uryga AK, Reinhold J, et al. Vascular smooth muscle cell senescence promotes atherosclerosis and features of plaque vulnerability. Atherosclerosis. 2015;**132**(20):1909-1919

[54] Gomez D, Owens GK. Smooth muscle cell phenotypic switching in atherosclerosis. Cardiovascular Research. 2012;**95**(2):156-164

[55] Ponticos M, Smith BD. Extracellular matrix synthesis in vascular disease. hypertension, and atherosclerosis. Journal of Biomedical Research. 2014;**28**(1):25-39

[56] Toma I, McCaffrey TA. Transforming growth factor-β and atherosclerosis: Interwoven atherogenic and atheroprotective aspects. Cell and Tissue Research. 2012;**347**(1):155-175

[57] Tedgui A, Mallat Z. Cytokines in atherosclerosis: Pathogenic and regulatory pathways. Physiological Reviews. 2006;**86**:515-581

[58] Brites F, Martin M, Guillas I, Kontush A. Antioxidative activity of high-density lipoprotein (HDL): Mechanistic insights into potential clinical benefit. BBA Clinical. 2017;**8**:66-77

[59] Singh K, Singh R, Chandra S, Tyagi S. Paraoxonase-1 is a better indicator than HDL of atherosclerosis—A pilot study in North Indian population. Diabetes and Metabolic Syndrome: Clinical Research and Reviews. 2018;**12**(3):275-268

[60] Peng ZY, Zhao SP, He BM, et al. Protective effect of HDL on endothelial NO production: The role of DDAH/ ADMA pathway. Molecular and Cellular Biochemistry. 2011;**351**(1-2):243-249

[61] Tran-Dinh A, Diallo D, Delbosc S, et al. HDL and endothelial protection. British Journal of Pharmacology. 2013;**169**(3):493-511

[62] Barter PJ, Nicholls S, Rye KA, et al. Antiinflammatory properties of HDL. Circulation Research. 2004;**95**:764-772

[63] Ganjali S, Gotto AM Jr, Ruscica M, et al. Monocyte-to-HDLcholesterol ratio as a prognostic marker in cardiovascular disease. Journal of Cellular Physiology. 2018;**233**(12):9237-9246

[64] van der Stoep M, Korporaai SJ, Van Eck M. High-density lipoprotein as a modulator of platelet and coagulation responses. Cardiovascular Research. 2014;**103**(3):362-371

[65] Phillips MC. Molecular mechanisms of cellular cholesterol efflux. The Journal of Biological Chemistry. 2014;**289**(35):24020-24029

[66] Yancey PG, Bortnick AE, Kellner-Weibel G, et al. Importance of different pathways of cellular cholesterol efflux. Arteriosclerosis, Thrombosis, and Vascular Biology. 2003;**23**(5):712-719

[67] Lee MK, Moore XL, Fu Y, et al. High-density lipoprotein inhibits human M1 macorphage polarization through redistribution of caveolin-1. British Journal of Pharmacology. 2016;**173**(4):741-751

[68] Sanson M, Distel E, Fisher EA. HDL induces the expression of the M2 macrophage markers arginase 1 and fizz-1 in a STAT6-depedent process. PLoS One. 2013;**8**(8):e74676

[69] Terasaka N, Wang N, Yvan-Charvet L, Tall AR. High-density lipoprotein protects macrophages from oxidized low-density lipoprotein-induced apoptosis by promoting efflux of 7-ketocholesterol via ABCG1. Proceedings of the National Academy

of Sciences of the United States of America. 2007;**104**(38):15093-15098

[70] Insull W Jr. The pathology of atherosclerosis. Plaque development and plaque responses to medical treatment. The American Journal of Medicine. 2009;**122**(1):S3-S14

[71] Sakakura K, Nakano M, Otsuka F, et al. Pathophysiology of atherosclerosis plaque progression. Heart, Lung Circulation. 2013;**22**(6):399-411

[72] Martinet W, Schrijvers DM, De Meyer GRY. Necrotic cell death in atherosclerosis. Basic Research in Cardiology. 2011;**106**:749-760

[73] Kojima Y, Weissman IL, Leeper NJ. The role of efferocytosis in atherosclerosis. Circulation. 2017;**135**:476-489

[74] Weinert S, Poitz DM, Auffermann-Gretzinger S, et al. The lysosomal transfer of LDL/cholesterol from macrophages into vascular smooth muscle cells induces their phenotypic alteration. Cardiovascular Research. 2013;**97**(3):544-542

[75] Singh RB, Mengi SA, Xu YJ, et al. Pathogenesis of atherosclerosis: A multifactorial process. Experimental and Clinical Cardiology. 2002;**7**(1):40-53

[76] Matsuo Y, Takumi T, Matthew V, et al. Plaque characteristics and arterial remodeling in coronary and peripheral arterial systems. Atherosclerosis. 2012;**223**(2):365-371

[77] van der Wal AC, Becker AE. Atherosclerotic plaque rupture— Pathologic basis of plaque stability and instability. Cardiovascular Research. 1999;**41**(2):334-344

[78] Halvorsen B, Otterdal K, Dahl TB, et al. Atherosclerotic plaque

stability—What determines the fate of a plaque? Progress in Cardiovascular Diseases. 2008;**51**(3):183-194

[79] Osborn EA, Jaffer FA. Imaging atherosclerosis and risk of plaque rupture. Current Atherosclerosis Reports. 2013;**15**(10):359

[80] Nadkarni SK, Bilenca A, Bouma BE, Tearney GJ. Measurement of fibrous cap thickness in athersclerotic plaques by spatiotemporal analysis of laser speckle images. Journal of Biomedical Optics. 2006;**11**(2):021006

[81] Newby AC. Metalloproteinases and vulnerable atherosclerotic plaques. Trends in Cardiovascular Medicine. 2007;**17**(8):253-258

[82] Johnson JL. Metalloproteinases in atherosclerosis. European Journal of Pharmacology. 2017;**816**:93-106

[83] Ruddy JM, Ikonomdis JS, Jones JA. Multidimensional contribution of matrix metalloproteinases to atherosclerotic plaque vulnerability: Multiple mechanisms of inhibition to promote stability. Journal of Vascular Research. 2015;**53**:1-16

[84] Clarke MC, Figg N, Maguire JJ, et al. Apoptosis of vascular smooth muscle cells induces features of plaque vulnerability in atherosclerosis. Nature Medicine. 2006;**12**:1075-1080

[85] Rohm I, Atiskova Y, Drobnik S, et al. Decreased regulatory T cells in vulnerable atherosclerotic lesions: Imbalance between pro- and antiinflammatory cells in atherosclerosis. Mediators of Inflammation. 2015;**2015**:364710

[86] Ammirati E, Moroni F, Magnoni M, Camici PG. The role of T and B cells in human atherosclerosis and atherothrombosis. Clinical and Experimental Immunology. 2015;**179**(2):173-187

**35**

*Dyslipidemia and Its Role in the Pathogenesis of Atherosclerotic Cardiovascular Disease…*

agents for the treatment of patients with atherothrombosis. Handbook of Experimental Pharmacology.

[97] van Montfoort ML, Kuijpers MJE, Knaup VL, et al. Factor XI regulates pathological thrombus formation on acutely ruptured atherosclerotic

Thrombosis, and Vascular Biology.

[98] Uchida Y, Uchida Y, Sakurai T, et al. Characterization of coronary fibrin thrombus in patients with acute coronary syndrome using dyestaining angioscopy. Arteriosclerosis, Thrombosis, and Vascular Biology.

[99] Niesten JM, van der Schaaf IC, van Dam L, et al. Histopathologic composition of cerebral thrombi of acute stroke patients is

correlated with stroke subtype and thrombus attenuation. PLoS One.

[100] Anderson TJ, Gregoire J, Pearson GJ, et al. 2016 Canadian Cardiovascular Society Guidelines for the management of dyslipidemia for the prevention of cardiovascular disease in the adult. The Canadian Journal of Cardiology.

[101] Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC/AACVPR/ AAPA/ABC/ACPM/ADA/AGS/ APhA/ASPC/NLA/PCNA Guideline on the management of blood cholesterol. Journal of the American College of Cardiology. 2018. pii:

2012;**210**:239-260

plaques. Arteriosclerosis,

2014;**34**:1668-1673

2011;**31**:1452-1460

2014;**9**(2):e88882

2016;**32**(11):1263-1282

S0735-1097(18)39033-8

2016;**37**(39):2999-3058

[102] Catapano AL, Graham I, De Backer G, et al. 2016 ESC/EAS Guidelines for the management of dyslipidaemias. European Heart Journal.

Barret C, et al. 2016 AHA/ACC

[103] Gerhard-Herman MD, Gornik HL,

*DOI: http://dx.doi.org/10.5772/intechopen.85772*

[87] Lafont A. Basic aspects of plaque vulnerability. Heart. 2003;**89**(10):

[88] Badimon L, Pardo T, Vilahur G. Atherosclerosis, platelets and thrombosis in acute ischaemic heart disease. European Heart Journal Acute Cardiovascular Care. 2012;**1**(1):60-74

[89] Sato Y, Hatakeyama K, Yamashita A, et al. Proportion of fibrin and platelets differs in thrombi on ruptured and eroded coronary atherosclerotic plaques in humans. Heart. 2005;**91**:526-530

[90] Olie RH, van der Meijden PEJ, ten Cate H. The coagulation system in atherothrombosis: Implications for new therapeutic strategies. Research and Practice in Thrombosis and Haemostasis. 2018;**2**:188-198

[91] Wu MD, Atkinson TM, Lindner JR.

Platelets and von Willebrand factor in atherogenesis. Blood. 2017;**129**(11):1415-1419

[92] Guo S, Shen S, Wang J, et al. Detection of high-risk atherosclerotic plaques with ultrasound molecular imaging of glycoprotein IIb/IIIa receptor on activated platelets. Theranostics.

[93] Bogousslavsky J. Benefit of ADP receptor antagonists in atherothrombotic patients: New evidence. Cerebrovascular Diseases.

[94] Moons AHM, Levi M, Peters RJG. Tissue factor and coronary artery disease. Cardiovascular Research.

[95] Tatsumi K, Machman N. Tissue factor and atherothrombosis. Journal of Atherosclerosis and Thrombosis.

[96] Leonardi S, Becker RC. PAR-1 inhibitors: A novel class of antiplatelet

2015;**5**(2):418-430

2011;**11**(Suppl 2):5-10

2002;**53**(2):313-325

2015;**22**(6):543-549

1262-1267

*Dyslipidemia and Its Role in the Pathogenesis of Atherosclerotic Cardiovascular Disease… DOI: http://dx.doi.org/10.5772/intechopen.85772*

[87] Lafont A. Basic aspects of plaque vulnerability. Heart. 2003;**89**(10): 1262-1267

*Dyslipidemia*

of Sciences of the United States of America. 2007;**104**(38):15093-15098

[70] Insull W Jr. The pathology of

2009;**122**(1):S3-S14

atherosclerosis. Plaque development and plaque responses to medical treatment. The American Journal of Medicine.

stability—What determines the fate of a plaque? Progress in Cardiovascular

[79] Osborn EA, Jaffer FA. Imaging atherosclerosis and risk of plaque rupture. Current Atherosclerosis

[80] Nadkarni SK, Bilenca A, Bouma BE, Tearney GJ. Measurement of fibrous cap thickness in athersclerotic plaques by spatiotemporal analysis of laser speckle images. Journal of Biomedical Optics.

[81] Newby AC. Metalloproteinases and vulnerable atherosclerotic plaques. Trends in Cardiovascular Medicine.

[82] Johnson JL. Metalloproteinases in atherosclerosis. European Journal of Pharmacology. 2017;**816**:93-106

[83] Ruddy JM, Ikonomdis JS, Jones JA. Multidimensional contribution of matrix metalloproteinases to atherosclerotic plaque vulnerability: Multiple mechanisms of inhibition to promote stability. Journal of Vascular

[84] Clarke MC, Figg N, Maguire JJ, et al. Apoptosis of vascular smooth muscle cells induces features of plaque vulnerability in atherosclerosis. Nature

[85] Rohm I, Atiskova Y, Drobnik S, et al. Decreased regulatory T cells in vulnerable atherosclerotic lesions: Imbalance between pro- and antiinflammatory cells in atherosclerosis.

[86] Ammirati E, Moroni F, Magnoni M, Camici PG. The role of T and B cells in human atherosclerosis and atherothrombosis. Clinical and Experimental Immunology.

Medicine. 2006;**12**:1075-1080

Mediators of Inflammation.

2015;**2015**:364710

2015;**179**(2):173-187

Diseases. 2008;**51**(3):183-194

Reports. 2013;**15**(10):359

2006;**11**(2):021006

2007;**17**(8):253-258

Research. 2015;**53**:1-16

[71] Sakakura K, Nakano M, Otsuka F, et al. Pathophysiology of atherosclerosis

plaque progression. Heart, Lung Circulation. 2013;**22**(6):399-411

[72] Martinet W, Schrijvers DM, De Meyer GRY. Necrotic cell death in atherosclerosis. Basic Research in Cardiology. 2011;**106**:749-760

[73] Kojima Y, Weissman IL, Leeper NJ.

[74] Weinert S, Poitz DM, Auffermann-Gretzinger S, et al. The lysosomal transfer of LDL/cholesterol from macrophages into vascular smooth muscle cells induces their phenotypic alteration. Cardiovascular Research.

[75] Singh RB, Mengi SA, Xu YJ, et al. Pathogenesis of atherosclerosis: A multifactorial process. Experimental

[76] Matsuo Y, Takumi T, Matthew V, et al. Plaque characteristics and arterial remodeling in coronary and peripheral arterial systems. Atherosclerosis.

[77] van der Wal AC, Becker AE. Atherosclerotic plaque rupture— Pathologic basis of plaque stability and instability. Cardiovascular Research.

[78] Halvorsen B, Otterdal K, Dahl TB, et al. Atherosclerotic plaque

The role of efferocytosis in atherosclerosis. Circulation.

2017;**135**:476-489

2013;**97**(3):544-542

and Clinical Cardiology.

2002;**7**(1):40-53

2012;**223**(2):365-371

1999;**41**(2):334-344

**34**

[88] Badimon L, Pardo T, Vilahur G. Atherosclerosis, platelets and thrombosis in acute ischaemic heart disease. European Heart Journal Acute Cardiovascular Care. 2012;**1**(1):60-74

[89] Sato Y, Hatakeyama K, Yamashita A, et al. Proportion of fibrin and platelets differs in thrombi on ruptured and eroded coronary atherosclerotic plaques in humans. Heart. 2005;**91**:526-530

[90] Olie RH, van der Meijden PEJ, ten Cate H. The coagulation system in atherothrombosis: Implications for new therapeutic strategies. Research and Practice in Thrombosis and Haemostasis. 2018;**2**:188-198

[91] Wu MD, Atkinson TM, Lindner JR. Platelets and von Willebrand factor in atherogenesis. Blood. 2017;**129**(11):1415-1419

[92] Guo S, Shen S, Wang J, et al. Detection of high-risk atherosclerotic plaques with ultrasound molecular imaging of glycoprotein IIb/IIIa receptor on activated platelets. Theranostics. 2015;**5**(2):418-430

[93] Bogousslavsky J. Benefit of ADP receptor antagonists in atherothrombotic patients: New evidence. Cerebrovascular Diseases. 2011;**11**(Suppl 2):5-10

[94] Moons AHM, Levi M, Peters RJG. Tissue factor and coronary artery disease. Cardiovascular Research. 2002;**53**(2):313-325

[95] Tatsumi K, Machman N. Tissue factor and atherothrombosis. Journal of Atherosclerosis and Thrombosis. 2015;**22**(6):543-549

[96] Leonardi S, Becker RC. PAR-1 inhibitors: A novel class of antiplatelet agents for the treatment of patients with atherothrombosis. Handbook of Experimental Pharmacology. 2012;**210**:239-260

[97] van Montfoort ML, Kuijpers MJE, Knaup VL, et al. Factor XI regulates pathological thrombus formation on acutely ruptured atherosclerotic plaques. Arteriosclerosis, Thrombosis, and Vascular Biology. 2014;**34**:1668-1673

[98] Uchida Y, Uchida Y, Sakurai T, et al. Characterization of coronary fibrin thrombus in patients with acute coronary syndrome using dyestaining angioscopy. Arteriosclerosis, Thrombosis, and Vascular Biology. 2011;**31**:1452-1460

[99] Niesten JM, van der Schaaf IC, van Dam L, et al. Histopathologic composition of cerebral thrombi of acute stroke patients is correlated with stroke subtype and thrombus attenuation. PLoS One. 2014;**9**(2):e88882

[100] Anderson TJ, Gregoire J, Pearson GJ, et al. 2016 Canadian Cardiovascular Society Guidelines for the management of dyslipidemia for the prevention of cardiovascular disease in the adult. The Canadian Journal of Cardiology. 2016;**32**(11):1263-1282

[101] Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC/AACVPR/ AAPA/ABC/ACPM/ADA/AGS/ APhA/ASPC/NLA/PCNA Guideline on the management of blood cholesterol. Journal of the American College of Cardiology. 2018. pii: S0735-1097(18)39033-8

[102] Catapano AL, Graham I, De Backer G, et al. 2016 ESC/EAS Guidelines for the management of dyslipidaemias. European Heart Journal. 2016;**37**(39):2999-3058

[103] Gerhard-Herman MD, Gornik HL, Barret C, et al. 2016 AHA/ACC

Guideline on the management of patients with lower extremity peripheral artery disease. Journal of the American College of Cardiology. 2017;**69**(11):e71-e126

[104] Levine GN, Bates ER, Bittl JA, et al. 2016 ACC/AHA Guideline focused update on duration of dual antiplatelet therapy in patients with coronary artery disease. Journal of the American College of Cardiology. 2016;**68**(10):1082-1115

[105] Levine GN, Bates ER, Blankenship JC, et al. 2015 ACC/AHA/SCAI focused update on primary percutaneous coronary intervention for patients with ST-elevation myocardial infarction. Journal of the American College of Cardiology. 2016;**67**(10):1235-1250

[106] Amsterdam EA, Wenger NK, Brindis RG, et al. 2014 AHA/ACC Guideline for the management of patients with non-ST-elevation acute coronary syndromes. Journal of the American College of Cardiology. 2014;**64**(24):e139-e228

[107] Fihn SD, Gardin JM, Abrams J, et al. 2012 ACC/AHA/ACP/AATS/ PCNA/SCAI/STS Guideline for the diagnosis and management of patients with stable ischemic heart disease. Journal of the American College of Cardiology. 2012;**60**(24):e44-e164

[108] Anderson JL, Halperin JL, Albert N, et al. Management of patients with peripheral artery disease (compilation of 2005 and 2011 ACCF/AHA Guideline recommendations). Journal of the American College of Cardiology. 2013;**61**(14):1555-1570

[109] O'Gara PT, Kushner FG, Ascheim DD, et al. 2013 ACCF/AHA Guideline for the management of ST-elevation myocardial infarction. Journal of the American College of Cardiology. 2013;**61**(4):e78-e140

[110] Smith SC Jr, Benjamin EJ, Bonow RO, et al. AHA/ACCF secondary

prevention and risk reduction therapy for patients with coronary and other atherosclerotic vascular disease: 2011 update. A guideline from the American Heart Association and American College of Cardiology Foundation endorsed by the World Heart Federation and the Preventive Cardiovascular Nurses Association. Journal of the American College of Cardiology. 2011;**58**(23):2432-2446

[111] Brott TG, Halperin JL, Abbara S, et al. 2011 ASA/ACCF/AHA/AANN/ AANS/ACR/ASNR/CNS/SAIP/SCAI/ SIR/SNIS/SVM/SVS Guideline on the management of patients with extracranial carotid and vertebral artery disease. Journal of the American College of Cardiology. 2011;**57**(8):e16-e94

[112] Powers WJ, Rabinstein AA, Ackerson T, et al. 2018 Guidelines for the early management of patients with acute ischemic stroke: A guideline for healthcare professionals from the American Heart Association/ American Stroke Association. Stroke. 2018;**49**:e46-e99

[113] Committee W, Das SR, Everett BM, Birtcher KK, et al. ACC expert consensus decision pathway on novel therapies for cardiovascular risk reduction in patients with type 2 diabetes and atherosclerotic cardiovascular disease. Journal of the American College of Cardiology. 2018;**2018**:25566. DOI: 10.1016/j. jacc.2018.09.020

[114] Llyod-Jones DM, Morris PB, Ballantyne CM, et al. 2017 Focused update on the 2016 ACC expert consensus decision pathway on the role of non-statin therapies for LDLcholesterol lowering in the management of atherosclerotic cardiovascular disease risk. Journal of the American College of Cardiology. 2017;**70**(14):1785-1822

[115] Thygesen K, Alpert JS, Jaffe AS, et al. Fourth universal definition of

**37**

*Dyslipidemia and Its Role in the Pathogenesis of Atherosclerotic Cardiovascular Disease…*

e9-e862.e14

2019;**132**(2):217-226

[123] Jangaard N, Sarkisian L, Saaby L, et al. Incidence, frequency, and clinical characteristics of type 3 myocardial infarction in clinical practice. American Journal of Medicine. 2017;**130**(7):862.

[124] Cediel G, Sandoval Y, Sexter A, et al. Risk estimation in type 2

myocardial infarction and myocardial injury: The TARRACO risk score. American Journal of Medicine.

[125] Hills LD, Smith PK, Anderson JL, et al. 2011 ACCF/AGA Guideline for coronary artery bypass graft surgery. Journal of the American College of Cardiology. 2011;**58**(24):e123-e210

[126] Levine GN, Bates ER, Blankenship

[127] Bashore TM, Balter S, Barac A, et al. 2012 American College of Cardiology Foundation/society for cardiovascular angiography and interventions expert consensus document on cardiac catheterization laboratory standards update. Journal of the American College of Cardiology.

[128] Banerjee C, Chimowitz MI. Stroke caused by atherosclerosis of the major intracranial arteries. Circulation Research. 2017;**120**:502-513

Epidemiology, risk factors, and clinical features of intracerebral hemorrhage:

[130] Woo D, Haverbusch M, Sekar P, et al. Effect of untreated hypertension on hemorrhagic stroke. Stroke.

JC, et al. 2011 ACCF/AHA/ SCAI Guideline for percutaneous coronary intervention. Journal of the American College of Cardiology.

2011;**58**(24):e44-e122

2012;**59**(24):2221-2305

[129] An SJ, Kim TJ, Yoon BW.

An update. Journal of Stroke.

2017;**19**(1):3-10

2004;**35**:1703-1708

*DOI: http://dx.doi.org/10.5772/intechopen.85772*

myocardial infarction. Journal of the American College of Cardiology. 2018;**2018**:25285. DOI: 10.1016/j.

[116] Ford TJ, Corcoran D, Berry C, et al. Stable coronary syndromes: Pathophysiology, diagnostic advances

[117] Ohman EM. Clinical practice. Chronic stable angina. New England Journal of Medicine. 2016;**374**(12):1167-1176

[118] Greenland P, Blaha M, Budoff MJ, Erbel R, Watson KE. Coronary calcium score and cardiovascular risk. Journal of the American College of Cardiology.

[119] Eisen A, Giugliano RP, Braunwald

syndrome: A review. JAMA Cardiology.

[120] Trzeciak P, Gierlotka M, Gasior M,

E. Updates on acute coronary

et al. In-hospital and 12-month outcomes after acute coronary syndrome treatment in patients aged <40 years of age (from the Polish Registry of Acute Coronary Syndromes). American Journal of Cardiology. 2014;**114**(2):175-180

[121] Puymirat E, Simon T, Cayla G, et al. Acute myocardial infarction: Changes in patient characteristics, management, and 6-month outcomes over a period of 20 years in the FAST-MI program (French Registry of Acute ST-Elevation or Non-ST-Elevation Myocardial Infarction 1995 to 2015). Circulation.

2017;**136**(20):1908-1919

2017;**55**(2):181-188

[122] Lippi G, Sanchis-Gomar F, Cervellin G. Cardiac troponins and mortality in type 1 and 2 myocardial infarction. Clinical Chemistry and Laboratory Medicine.

and therapeutic need. Heart.

2018;**72**(4):4343-4447

2016;**1**(6):718-730

jacc.2018.08.1038

2017;**0**:1-9

*Dyslipidemia and Its Role in the Pathogenesis of Atherosclerotic Cardiovascular Disease… DOI: http://dx.doi.org/10.5772/intechopen.85772*

myocardial infarction. Journal of the American College of Cardiology. 2018;**2018**:25285. DOI: 10.1016/j. jacc.2018.08.1038

*Dyslipidemia*

Guideline on the management of patients with lower extremity peripheral artery disease. Journal of the American College of Cardiology. prevention and risk reduction therapy for patients with coronary and other atherosclerotic vascular disease: 2011 update. A guideline from the American Heart Association and American College of Cardiology Foundation endorsed by the World Heart Federation and the Preventive Cardiovascular Nurses Association. Journal of the American College of Cardiology.

[111] Brott TG, Halperin JL, Abbara S, et al. 2011 ASA/ACCF/AHA/AANN/ AANS/ACR/ASNR/CNS/SAIP/SCAI/ SIR/SNIS/SVM/SVS Guideline on the management of patients with extracranial carotid and vertebral artery disease. Journal of the American College of Cardiology. 2011;**57**(8):e16-e94

[112] Powers WJ, Rabinstein AA, Ackerson T, et al. 2018 Guidelines for the early management of patients with acute ischemic stroke: A guideline for healthcare professionals from the American Heart Association/ American Stroke Association. Stroke.

[113] Committee W, Das SR, Everett BM,

Birtcher KK, et al. ACC expert consensus decision pathway on novel therapies for cardiovascular risk reduction in patients with type 2 diabetes and atherosclerotic cardiovascular disease. Journal of the American College of Cardiology. 2018;**2018**:25566. DOI: 10.1016/j.

[114] Llyod-Jones DM, Morris PB, Ballantyne CM, et al. 2017 Focused update on the 2016 ACC expert consensus decision pathway on the role of non-statin therapies for LDLcholesterol lowering in the management of atherosclerotic cardiovascular disease risk. Journal of the American College of Cardiology. 2017;**70**(14):1785-1822

[115] Thygesen K, Alpert JS, Jaffe AS, et al. Fourth universal definition of

2018;**49**:e46-e99

jacc.2018.09.020

2011;**58**(23):2432-2446

[104] Levine GN, Bates ER, Bittl JA, et al. 2016 ACC/AHA Guideline focused update on duration of dual antiplatelet therapy in patients with coronary artery disease. Journal of the American College of Cardiology. 2016;**68**(10):1082-1115

[105] Levine GN, Bates ER, Blankenship JC, et al. 2015 ACC/AHA/SCAI focused update on primary percutaneous coronary intervention for patients with ST-elevation myocardial infarction. Journal of the American College of Cardiology. 2016;**67**(10):1235-1250

[106] Amsterdam EA, Wenger NK, Brindis RG, et al. 2014 AHA/ACC Guideline for the management of patients with non-ST-elevation acute coronary syndromes. Journal of the American College of Cardiology.

[107] Fihn SD, Gardin JM, Abrams J, et al. 2012 ACC/AHA/ACP/AATS/ PCNA/SCAI/STS Guideline for the diagnosis and management of patients with stable ischemic heart disease. Journal of the American College of Cardiology. 2012;**60**(24):e44-e164

[108] Anderson JL, Halperin JL, Albert N, et al. Management of patients with peripheral artery disease (compilation of 2005 and 2011 ACCF/AHA Guideline recommendations). Journal of the American College of Cardiology.

[109] O'Gara PT, Kushner FG, Ascheim DD, et al. 2013 ACCF/AHA Guideline for the management of ST-elevation myocardial infarction. Journal of the American College of Cardiology.

[110] Smith SC Jr, Benjamin EJ, Bonow RO, et al. AHA/ACCF secondary

2014;**64**(24):e139-e228

2013;**61**(14):1555-1570

2013;**61**(4):e78-e140

2017;**69**(11):e71-e126

**36**

[116] Ford TJ, Corcoran D, Berry C, et al. Stable coronary syndromes: Pathophysiology, diagnostic advances and therapeutic need. Heart. 2017;**0**:1-9

[117] Ohman EM. Clinical practice. Chronic stable angina. New England Journal of Medicine. 2016;**374**(12):1167-1176

[118] Greenland P, Blaha M, Budoff MJ, Erbel R, Watson KE. Coronary calcium score and cardiovascular risk. Journal of the American College of Cardiology. 2018;**72**(4):4343-4447

[119] Eisen A, Giugliano RP, Braunwald E. Updates on acute coronary syndrome: A review. JAMA Cardiology. 2016;**1**(6):718-730

[120] Trzeciak P, Gierlotka M, Gasior M, et al. In-hospital and 12-month outcomes after acute coronary syndrome treatment in patients aged <40 years of age (from the Polish Registry of Acute Coronary Syndromes). American Journal of Cardiology. 2014;**114**(2):175-180

[121] Puymirat E, Simon T, Cayla G, et al. Acute myocardial infarction: Changes in patient characteristics, management, and 6-month outcomes over a period of 20 years in the FAST-MI program (French Registry of Acute ST-Elevation or Non-ST-Elevation Myocardial Infarction 1995 to 2015). Circulation. 2017;**136**(20):1908-1919

[122] Lippi G, Sanchis-Gomar F, Cervellin G. Cardiac troponins and mortality in type 1 and 2 myocardial infarction. Clinical Chemistry and Laboratory Medicine. 2017;**55**(2):181-188

[123] Jangaard N, Sarkisian L, Saaby L, et al. Incidence, frequency, and clinical characteristics of type 3 myocardial infarction in clinical practice. American Journal of Medicine. 2017;**130**(7):862. e9-e862.e14

[124] Cediel G, Sandoval Y, Sexter A, et al. Risk estimation in type 2 myocardial infarction and myocardial injury: The TARRACO risk score. American Journal of Medicine. 2019;**132**(2):217-226

[125] Hills LD, Smith PK, Anderson JL, et al. 2011 ACCF/AGA Guideline for coronary artery bypass graft surgery. Journal of the American College of Cardiology. 2011;**58**(24):e123-e210

[126] Levine GN, Bates ER, Blankenship JC, et al. 2011 ACCF/AHA/ SCAI Guideline for percutaneous coronary intervention. Journal of the American College of Cardiology. 2011;**58**(24):e44-e122

[127] Bashore TM, Balter S, Barac A, et al. 2012 American College of Cardiology Foundation/society for cardiovascular angiography and interventions expert consensus document on cardiac catheterization laboratory standards update. Journal of the American College of Cardiology. 2012;**59**(24):2221-2305

[128] Banerjee C, Chimowitz MI. Stroke caused by atherosclerosis of the major intracranial arteries. Circulation Research. 2017;**120**:502-513

[129] An SJ, Kim TJ, Yoon BW. Epidemiology, risk factors, and clinical features of intracerebral hemorrhage: An update. Journal of Stroke. 2017;**19**(1):3-10

[130] Woo D, Haverbusch M, Sekar P, et al. Effect of untreated hypertension on hemorrhagic stroke. Stroke. 2004;**35**:1703-1708

[131] Prabhakaran S, Ruff I, Bernstein RA. Acute stroke intervention: A systematic review. Journal of the American Medical Association. 2015;**313**(14):1451-1462

[132] Ceornodolea AD, Bal R, Severens JL. Epidemiology and management of atrial fibrillation and stroke: Review of data from four European countries. Stroke Research and Treatment. 2017;**2017**:8593207

[133] Smith EE, Kent DM, Bulsara KR, et al. Accuracy of prediction instruments for diagnosing large vessel occlusion in individuals with suspected stroke: A systematic review for the 2018 Guidelines for the early management of patients with acute ischemic stroke. Stroke. 2018;**49**:e111-e122

[134] Meschia JF, Bushnell C, Boden-Albala B, et al. Guidelines for the primary prevention of stroke: A statement for healthcare professionals from the American Heart Association/ American Stroke Association. Stroke. 2014;**45**:3754-3832

[135] Hiatt WR, Goldstone J, Smith SC Jr, et al. Atherosclerotic peripheral vascular disease symposium II: Nomenclature for vascular diseases. Circulation. 2008;**118**:2826-2829

[136] Kullo IJ, Rooke TW. Clinical practice. Peripheral artery disease. New England Journal of Medicine. 2016;**374**(9):861-871

[137] Creager MA, Kaufman JA, Conte MS. Clinical practice. Acute limb ischemia. New England Journal of Medicine. 2012;**366**:2198-2206

[138] Enezate TH, Omran J, Mahmud E, et al. Endovascular versus surgical treatment for acute limb ischemia: A systematic review and meta-analysis of clinical trials. Cardiovascular Diagnosis and Therapy. 2017;**7**(3):264-271

[139] Theodoridis PG, Davos CH, Dodos I, et al. Thrombolysis in acute lower limb ischemia. Review of the current literature. Annals of Vascular Surgery. 2018;**52**:255-262

[140] Kinlay SK. Management of critical limb ischemia. Circulation. Cardiovascular Interventions. 2016;**9**(2):e001946

[141] Fabiani I, Calogero E, Pugliese NR, et al. Critical limb ischemia: A practical up-to-date review. Angiology. 2018;**69**(6):465-474

[142] Teraa M, Conte MS, Moll FL, Verhaar MC. Critical limb ischemia: Current trends and future directions. Journal of the American Heart Association. 2016;**5**:e002938

[143] Pollak AW, Norton P, Kramer CM. Multimodality imaging of lower extremity peripheral arterial disease: Current role and future directions. Circulation. Cardiovascular Imaging. 2012;**5**(6):797-807

[144] Shishehbor MH, White CJ, Gray BH, et al. Critical limb ischemia: An expert statement. Journal of the American College of Cardiology. 2016;**68**(16):2002-2015

[145] Walker TG. Acute limb ischemia. Techniques in Vascular and Interventional Radiology. 2009;**12**(2):117-129

[146] Weber BR, Dieter RS. Renal artery stenosis: Epidemiology and treatment. Iternational Journal of Nephrology and Renovascular Disease An international. 2014;**7**:169-181

[147] Gottam N, Nanjundappa A, Dieter RS. Renal artery stenosis: Pathophysiology and treatment. Expert Review of Cardiovascular Therapy. 2009;**7**(11):1413-1420

**39**

*Dyslipidemia and Its Role in the Pathogenesis of Atherosclerotic Cardiovascular Disease…*

independent disease to atherosclerosis? Cardiovascular Pathology. 2017;**27**:71-75

[158] Hong H, Yang Y, Liu B, Cai W. Imaging of abdominal aortic

[159] Goldstein JL, Brown MS. A century of cholesterol and coronaries: From plaques to genes to statins. Cell.

2010;**8**(6):808-819

2015;**161**(1):161-172

9-19

aneurysm: The present and the future. Current Vascular Pharmacology.

[160] Perak AM, Ning H, de Ferranti SD, et al. Long-term risk of atherosclerotic cardiovascular disease in US adults with the familial hypercholesterolemia phenotype. Circulation. 2016;**134**(1):

[161] Ogura M, Hori M, Harada-Shiba M.

Association between cholesterol efflux capacity and atherosclerotic cardiovascular disease in patients with familial hypercholesterolemia. Arteriosclerosis, Thrombosis, and Vascular Biology. 2016;**36**(1):181-188

[162] Emerging Risk Factors Collaboration, Di Angelantonio E, Gao P, et al. Lipid-related markers and cardiovascular disease prediciton. Journal of the American Medical Association. 2012;**307**:2499-2506

2010;**376**:1670-1681

[163] Cholesterol Treatment Trialists' (CTT) Collaboration, Baigent C, Blackwell L, et al. Efficacy and safety of more intensive lowering of LDL cholesterol: A meta-analysis of data from 170,000 participants in 26 randomized trials. Lancet.

[164] Nissen SE, Nicholls SJ, Sipahi I, et al. Effect of very high-intensity statin therapy on regression of coronary atherosclerosis: The ASTEROID trial. Journal of the American Medical Association. 2006;**295**:1556-1565

[165] Egede LE, Zheng D. Modifiable cardiovascular risk factors in adults

*DOI: http://dx.doi.org/10.5772/intechopen.85772*

ischemic nephropathy. Circulation.

[149] AbuRahma AF, Yacoub M. Renal

computed tomography angiography, magnestic resonance angiography, and angiography. Seminars in Vascular

[150] Bavishi C, de Leeuw PW, Messerli FH. Atherosclerotic renal artery

stenosis and hypertension: Pragmatism, pitfalls, and perspectives. American Journal of Medicine. 2016;**129**(6):635.

[151] Tafur JD, White CJ. Renal artery stenosis: When to revascularize in 2017. Current Problems in Cardiology.

[152] Hohenwalter EJ. Chronic mesenteric ischemia: Diagnosis and treatment. Seminars in Interventional

Radiology. 2009;**26**(4):345-351

[153] Zettervall SL, Lo RC, Soden PA, et al. Trends in treatment and mortality for mesenteric ischemia in the United States from 2000-2012. Annals of Vascular Surgery. 2017;**42**:111-119

[154] Bala M, Kashuk J, Moore EE, et al. Acute mesenteric ischemia: Guidelines of the world society of emergency surgery. World Journal of Emergency

[155] Dhatt HS, Behr SC, Miracle A, Wang ZJ, Yeh BM. Radiological evaluation of bowel ischemia. Radiologic Clinics of North America.

[156] Tilsed JVT, Casamassima A, Kurihara H, et al. ESTES Guidelines: Acute mesenteric ischemia. European Journal of Trauma and Emergency

[157] Toghill BJ, Saratzis A, Brown MJ. Abdominal Aortic Aneurysm—An

imaging: Duplex ultrasound,

Surgery. 2013;**26**(4):134-143

2005;**112**:1362-1374

e5-635.e14

2017;**42**(4):110-135

Surgery. 2017;**12**:38

2015;**53**(6):1241-1254

Surgery. 2016;**42**:253-270

[148] Garovic VD, Textor SC. Renovascular hypertension and *Dyslipidemia and Its Role in the Pathogenesis of Atherosclerotic Cardiovascular Disease… DOI: http://dx.doi.org/10.5772/intechopen.85772*

ischemic nephropathy. Circulation. 2005;**112**:1362-1374

*Dyslipidemia*

[131] Prabhakaran S, Ruff I, Bernstein RA. Acute stroke intervention: A systematic review. Journal of the American Medical Association.

[139] Theodoridis PG, Davos CH, Dodos I, et al. Thrombolysis in acute lower limb ischemia. Review of the current literature. Annals of Vascular Surgery.

[141] Fabiani I, Calogero E, Pugliese NR,

practical up-to-date review. Angiology.

[143] Pollak AW, Norton P, Kramer CM. Multimodality imaging of lower extremity peripheral arterial disease: Current role and future directions. Circulation. Cardiovascular Imaging.

[144] Shishehbor MH, White CJ, Gray BH, et al. Critical limb ischemia: An expert statement. Journal of the American College of Cardiology.

[146] Weber BR, Dieter RS. Renal artery stenosis: Epidemiology and treatment. Iternational Journal of Nephrology and Renovascular Disease An international.

Pathophysiology and treatment. Expert Review of Cardiovascular Therapy.

[147] Gottam N, Nanjundappa A, Dieter RS. Renal artery stenosis:

[140] Kinlay SK. Management of critical limb ischemia. Circulation. Cardiovascular Interventions.

et al. Critical limb ischemia: A

[142] Teraa M, Conte MS, Moll FL, Verhaar MC. Critical limb ischemia: Current trends and future directions. Journal of the American Heart Association. 2016;**5**:e002938

2018;**52**:255-262

2016;**9**(2):e001946

2018;**69**(6):465-474

2012;**5**(6):797-807

2016;**68**(16):2002-2015

2009;**12**(2):117-129

2014;**7**:169-181

2009;**7**(11):1413-1420

[148] Garovic VD, Textor SC. Renovascular hypertension and

[145] Walker TG. Acute limb ischemia. Techniques in Vascular and Interventional Radiology.

[132] Ceornodolea AD, Bal R, Severens JL. Epidemiology and management of atrial fibrillation and stroke: Review of data from four European countries. Stroke Research and Treatment.

[133] Smith EE, Kent DM, Bulsara KR,

instruments for diagnosing large vessel occlusion in individuals with suspected stroke: A systematic review for the 2018 Guidelines for the early management of patients with acute ischemic stroke.

[134] Meschia JF, Bushnell C, Boden-Albala B, et al. Guidelines for the primary prevention of stroke: A statement for healthcare professionals from the American Heart Association/ American Stroke Association. Stroke.

[135] Hiatt WR, Goldstone J, Smith SC Jr, et al. Atherosclerotic peripheral vascular disease symposium II: Nomenclature for vascular diseases. Circulation.

[136] Kullo IJ, Rooke TW. Clinical practice. Peripheral artery disease. New England Journal of Medicine.

[137] Creager MA, Kaufman JA, Conte MS. Clinical practice. Acute limb ischemia. New England Journal of Medicine. 2012;**366**:2198-2206

[138] Enezate TH, Omran J, Mahmud E, et al. Endovascular versus surgical treatment for acute limb ischemia: A systematic review and meta-analysis of clinical trials. Cardiovascular Diagnosis

and Therapy. 2017;**7**(3):264-271

et al. Accuracy of prediction

Stroke. 2018;**49**:e111-e122

2014;**45**:3754-3832

2008;**118**:2826-2829

2016;**374**(9):861-871

2015;**313**(14):1451-1462

2017;**2017**:8593207

**38**

[149] AbuRahma AF, Yacoub M. Renal imaging: Duplex ultrasound, computed tomography angiography, magnestic resonance angiography, and angiography. Seminars in Vascular Surgery. 2013;**26**(4):134-143

[150] Bavishi C, de Leeuw PW, Messerli FH. Atherosclerotic renal artery stenosis and hypertension: Pragmatism, pitfalls, and perspectives. American Journal of Medicine. 2016;**129**(6):635. e5-635.e14

[151] Tafur JD, White CJ. Renal artery stenosis: When to revascularize in 2017. Current Problems in Cardiology. 2017;**42**(4):110-135

[152] Hohenwalter EJ. Chronic mesenteric ischemia: Diagnosis and treatment. Seminars in Interventional Radiology. 2009;**26**(4):345-351

[153] Zettervall SL, Lo RC, Soden PA, et al. Trends in treatment and mortality for mesenteric ischemia in the United States from 2000-2012. Annals of Vascular Surgery. 2017;**42**:111-119

[154] Bala M, Kashuk J, Moore EE, et al. Acute mesenteric ischemia: Guidelines of the world society of emergency surgery. World Journal of Emergency Surgery. 2017;**12**:38

[155] Dhatt HS, Behr SC, Miracle A, Wang ZJ, Yeh BM. Radiological evaluation of bowel ischemia. Radiologic Clinics of North America. 2015;**53**(6):1241-1254

[156] Tilsed JVT, Casamassima A, Kurihara H, et al. ESTES Guidelines: Acute mesenteric ischemia. European Journal of Trauma and Emergency Surgery. 2016;**42**:253-270

[157] Toghill BJ, Saratzis A, Brown MJ. Abdominal Aortic Aneurysm—An

independent disease to atherosclerosis? Cardiovascular Pathology. 2017;**27**:71-75

[158] Hong H, Yang Y, Liu B, Cai W. Imaging of abdominal aortic aneurysm: The present and the future. Current Vascular Pharmacology. 2010;**8**(6):808-819

[159] Goldstein JL, Brown MS. A century of cholesterol and coronaries: From plaques to genes to statins. Cell. 2015;**161**(1):161-172

[160] Perak AM, Ning H, de Ferranti SD, et al. Long-term risk of atherosclerotic cardiovascular disease in US adults with the familial hypercholesterolemia phenotype. Circulation. 2016;**134**(1): 9-19

[161] Ogura M, Hori M, Harada-Shiba M. Association between cholesterol efflux capacity and atherosclerotic cardiovascular disease in patients with familial hypercholesterolemia. Arteriosclerosis, Thrombosis, and Vascular Biology. 2016;**36**(1):181-188

[162] Emerging Risk Factors Collaboration, Di Angelantonio E, Gao P, et al. Lipid-related markers and cardiovascular disease prediciton. Journal of the American Medical Association. 2012;**307**:2499-2506

[163] Cholesterol Treatment Trialists' (CTT) Collaboration, Baigent C, Blackwell L, et al. Efficacy and safety of more intensive lowering of LDL cholesterol: A meta-analysis of data from 170,000 participants in 26 randomized trials. Lancet. 2010;**376**:1670-1681

[164] Nissen SE, Nicholls SJ, Sipahi I, et al. Effect of very high-intensity statin therapy on regression of coronary atherosclerosis: The ASTEROID trial. Journal of the American Medical Association. 2006;**295**:1556-1565

[165] Egede LE, Zheng D. Modifiable cardiovascular risk factors in adults

with diabetes: Prevalence and missed opportunities for physician counseling. Archives of Internal Medicine. 2002;**162**(4):427-433

[166] Huma S, Tariq R, Amin F, Mahmood KJ. Modifiable and nonmodifiable predisposing risk factors of myocardial infarction—A review. Journal of Pharmaceutical Sciences and Research. 2012;**4**(1):1649-1653

[167] Yang EH. Lipid management guidelines. Medscape Cardiology. 2018. Available form: https://emedicine. medscape.com/article/2500032 overview [Accessed January 11, 2019]

[168] Zeadin MG, Petlura CI, Werstuck GH. Molecular mechanisms linking diabetes to the accelerated development of atherosclerosis. Canadian Journal of Diabetes. 2013;**37**(5):345-350

[169] Shah MS, Brownlee M. Molecular and cellular mechanisms of cardiovascular disorders in diabetes. Circulation Research. 2016;**118**(11):1808-1829

[170] Kanter JE, Kramer F, Barnhart S, et al. Diabetes promotes an inflammatory macrophage phenotype and atherosclerosis through Acyl-CoA sythetase 1. Proceedings of the National Academy of Sciences of the United States of America. 2012;**109**(12):E715-E724

[171] Virmani R, Burke AP, Kolodgie F. Morphological characteristics of coronary atherosclerosis in diabetes mellitus. Canadian Journal of Cardiology. 2006;**22**(Suppl B):81B-84B

[172] Wadhera RK, Steen DL, Khan I, et al. A review of low-density lipoprotein cholesterol, treatment strategies, and its impact on cardiovascular disease morbidity and mortality. Journal of Clinical Lipidology. 2016;**10**(3):472-489

[173] Koskinas KC, Siontis GCM, Piccolo R, et al. Effect of statins and non-statin LDL-lowering medications on cardiovascular outcomes in secondary prevention: A meta-analysis of randomized trials. European Heart Journal. 2018;**39**(14):1172-1180

[174] Satoh M, Takahashi Y, Tabuchi T, et al. Cellular and molecular mechanisms of satins: An update on pleiotropic effects. Clinical Science (London, England). 2015;**129**(2):93-105

[175] Lee SE, Chang HJ, Sung JM, et al. Effects on statins on coronary atherosclerotic plaques: The PARADIGM study. JACC: Cardiovascular Imaging. 2018;**11**(10):1475-1484

[176] Yla-Herttula S, Bentzon JF, Daemen M, et al. Stabilization of atherosclerotic plaques: An update. European Heart Journal. 2013;**34**:3251-3258

[177] Vavlukis M, Vavlukis A. Adding ezetimibe to statin therapy: Latest evidence and clinical implications. Drugs in Context. 2018;**7**:212534

[178] Bogiatzi C, Spence JD. Ezetimibe and regression of carotid atherosclerosis: Importance of measuring plaque burden. Stroke. 2012;**43**(4):1153-1155

[179] Ueda Y, Hiro T, Hirayama A, et al. Effect of ezetimibe on stabilization and regression of intracoronary plaque—The ZIPANGU study. Circulation Journal. 2017;**81**(11):1611-1619

[180] Shapiro MD, Fazio S. PSCK9 and atherosclerosis—Lipids and beyond. Journal of Atherosclerosis and Thrombosis. 2017;**24**:462-472

[181] Ikegami Y, Inoue I, Inoue K, et al. The annual rate of coronary artery calcification with combination

**41**

*Dyslipidemia and Its Role in the Pathogenesis of Atherosclerotic Cardiovascular Disease…*

[189] Zeleny M, Swertfeger DK, Weisgraber KH, Hui DY. Distinct apolipoprotein E isoform preference for inhibition of smooth muscle cell migration and proliferation. Biochemistry. 2002;**41**(39):11820-11823

[190] Yue L, Bian JT, Grizelj I, et al. ApoE enhances endothelial-NO production by modulating caveolin-1 interaction with eNOS. Hypertension.

[192] Tardif JC, McMurray JJ, Klug E, et al. Effects of succinobucol (AGI-1067) after an acute coronary syndrome: A randomised, doubleblind, placebo-controlled trial. Lancet.

2012;**60**(4):1040-1046

2011;**10**(5):365-376

[191] Charo IS, Taub R. Antiinflammatory therpeutics for the treatment of atherosclerosis. Nature Reviews. Drug Discovery.

2008;**371**(9626):1761-1768

2010;**21**(6):473-480

[193] Rosenson RS. Phospholipase A2 inhibition and atherosclerotic vascular disease: Prospects for targeting secretory and lipoproteinassociated phospholipase A2 enzymes. Current Opinion in Lipidology.

[194] Riccioni G, Zanasi A, Vitulano N, et al. Leukotrienes in atherosclerosis: New target inisights and future therapy perspectives. Mediators of Inflammation. 2009;**2009**:737282

[195] Lin J, Kakkar V, Lu X. Impact of MCP-1 in atherosclerosis. Current Pharmaceutical Design.

[196] Tousoulis D, Oikonomou E, Economou EK, et al. Inflammatory cytokines in atherosclerosis: Current therapeutic approaches. European Heart

2014;**20**(28):4580-4588

Journal. 2016;**37**:1723-1735

*DOI: http://dx.doi.org/10.5772/intechopen.85772*

therapy with a PSCK9 inhibitor and a statin is lower than that with statin monotherapy. NPJ Aging and Mechanisms of Disease. 2018;**4**:7

[182] Kuhnast S, van der Hoorn JWA, Pieterman EJ, et al. Alirocumab inhibits atherosclerosis, improves the plaque morphology, and enhances the effects of a statin. Journal of Lipid Research.

[183] Lacy M, Atzler D, Liu R, et al. Interactions between dyslipidemia and the immune system and their relevance as putative therapeutic

[184] Valanti EK, Dalakoura-Karagkouni K, Sanoudoi D. Current and emerging reconstituted HDL-apoA-I and HDLapoE approaches to treat atherosclerosis. Journal of Personalized Medicine.

[185] Wu D, Sharan C, Yang H, et al. Apolipoprotein E-deficient lipoproteins induce foam cell formation by downregulation of lysosomal hydrolases in macrophages.

Journal of Lipid Research. 2007;**48**(12):2571-2578

2001;**276**(49):46011-46016

[186] Stannard AK, Riddell DR, Sacre SM, et al. Cell-derived Apolipoprotein E (ApoE) particles inhibit vascular cell adhesion molecule-1 (VCAM-1) expression in human endothelial cells. The Journal of Biological Chemistry.

[187] Mallat Z, Taleb S, Ait-Oufella H, Tedgui A. The role of adaptive T cell immunity in atherosclerosis. Journal of Lipid Research. 2009;**50**(Suppl):S364-S369

[188] Dose J, Huebble P, Nebel A, Rimbach G. APOE genotype and stress response—A mini review. Lipids in Health and Disease. 2016;**15**:121

2014;**55**(10):2103-2112

targets in atherosclerosis. Pharmacology & Therapeutics.

2019;**193**:50-62

2018;**8**:34

*Dyslipidemia and Its Role in the Pathogenesis of Atherosclerotic Cardiovascular Disease… DOI: http://dx.doi.org/10.5772/intechopen.85772*

therapy with a PSCK9 inhibitor and a statin is lower than that with statin monotherapy. NPJ Aging and Mechanisms of Disease. 2018;**4**:7

*Dyslipidemia*

with diabetes: Prevalence and missed opportunities for physician counseling. [173] Koskinas KC, Siontis GCM, Piccolo R, et al. Effect of statins and non-statin LDL-lowering medications

on cardiovascular outcomes in

et al. Cellular and molecular

secondary prevention: A meta-analysis of randomized trials. European Heart Journal. 2018;**39**(14):1172-1180

[174] Satoh M, Takahashi Y, Tabuchi T,

mechanisms of satins: An update on pleiotropic effects. Clinical Science (London, England). 2015;**129**(2):93-105

[175] Lee SE, Chang HJ, Sung JM, et al. Effects on statins on coronary atherosclerotic

plaques: The PARADIGM study. JACC: Cardiovascular Imaging.

[176] Yla-Herttula S, Bentzon JF, Daemen M, et al. Stabilization of atherosclerotic plaques: An update. European Heart Journal.

[177] Vavlukis M, Vavlukis A. Adding ezetimibe to statin therapy: Latest evidence and clinical implications. Drugs in Context. 2018;**7**:212534

[178] Bogiatzi C, Spence JD. Ezetimibe

[179] Ueda Y, Hiro T, Hirayama A, et al. Effect of ezetimibe on stabilization and regression of intracoronary plaque—The ZIPANGU study. Circulation Journal.

[180] Shapiro MD, Fazio S. PSCK9 and atherosclerosis—Lipids and beyond. Journal of Atherosclerosis and

Thrombosis. 2017;**24**:462-472

[181] Ikegami Y, Inoue I, Inoue K, et al. The annual rate of coronary artery calcification with combination

and regression of carotid atherosclerosis: Importance of measuring plaque burden. Stroke.

2012;**43**(4):1153-1155

2017;**81**(11):1611-1619

2018;**11**(10):1475-1484

2013;**34**:3251-3258

Archives of Internal Medicine.

[166] Huma S, Tariq R, Amin F, Mahmood KJ. Modifiable and nonmodifiable predisposing risk factors of myocardial infarction—A review. Journal of Pharmaceutical Sciences and

Research. 2012;**4**(1):1649-1653

[167] Yang EH. Lipid management guidelines. Medscape Cardiology. 2018. Available form: https://emedicine. medscape.com/article/2500032 overview [Accessed January 11, 2019]

[168] Zeadin MG, Petlura CI, Werstuck GH. Molecular mechanisms linking diabetes to the accelerated development of atherosclerosis. Canadian Journal of

[169] Shah MS, Brownlee M. Molecular

[170] Kanter JE, Kramer F, Barnhart S,

inflammatory macrophage phenotype and atherosclerosis through Acyl-CoA sythetase 1. Proceedings of the National Academy of Sciences of the United States of America.

[171] Virmani R, Burke AP, Kolodgie F. Morphological characteristics of coronary atherosclerosis in diabetes mellitus. Canadian Journal of

Cardiology. 2006;**22**(Suppl B):81B-84B

[172] Wadhera RK, Steen DL, Khan I, et al. A review of low-density lipoprotein cholesterol, treatment strategies, and its impact on

cardiovascular disease morbidity and mortality. Journal of Clinical Lipidology.

Diabetes. 2013;**37**(5):345-350

and cellular mechanisms of cardiovascular disorders in diabetes. Circulation Research.

2016;**118**(11):1808-1829

et al. Diabetes promotes an

2012;**109**(12):E715-E724

2002;**162**(4):427-433

**40**

2016;**10**(3):472-489

[182] Kuhnast S, van der Hoorn JWA, Pieterman EJ, et al. Alirocumab inhibits atherosclerosis, improves the plaque morphology, and enhances the effects of a statin. Journal of Lipid Research. 2014;**55**(10):2103-2112

[183] Lacy M, Atzler D, Liu R, et al. Interactions between dyslipidemia and the immune system and their relevance as putative therapeutic targets in atherosclerosis. Pharmacology & Therapeutics. 2019;**193**:50-62

[184] Valanti EK, Dalakoura-Karagkouni K, Sanoudoi D. Current and emerging reconstituted HDL-apoA-I and HDLapoE approaches to treat atherosclerosis. Journal of Personalized Medicine. 2018;**8**:34

[185] Wu D, Sharan C, Yang H, et al. Apolipoprotein E-deficient lipoproteins induce foam cell formation by downregulation of lysosomal hydrolases in macrophages. Journal of Lipid Research. 2007;**48**(12):2571-2578

[186] Stannard AK, Riddell DR, Sacre SM, et al. Cell-derived Apolipoprotein E (ApoE) particles inhibit vascular cell adhesion molecule-1 (VCAM-1) expression in human endothelial cells. The Journal of Biological Chemistry. 2001;**276**(49):46011-46016

[187] Mallat Z, Taleb S, Ait-Oufella H, Tedgui A. The role of adaptive T cell immunity in atherosclerosis. Journal of Lipid Research. 2009;**50**(Suppl):S364-S369

[188] Dose J, Huebble P, Nebel A, Rimbach G. APOE genotype and stress response—A mini review. Lipids in Health and Disease. 2016;**15**:121

[189] Zeleny M, Swertfeger DK, Weisgraber KH, Hui DY. Distinct apolipoprotein E isoform preference for inhibition of smooth muscle cell migration and proliferation. Biochemistry. 2002;**41**(39):11820-11823

[190] Yue L, Bian JT, Grizelj I, et al. ApoE enhances endothelial-NO production by modulating caveolin-1 interaction with eNOS. Hypertension. 2012;**60**(4):1040-1046

[191] Charo IS, Taub R. Antiinflammatory therpeutics for the treatment of atherosclerosis. Nature Reviews. Drug Discovery. 2011;**10**(5):365-376

[192] Tardif JC, McMurray JJ, Klug E, et al. Effects of succinobucol (AGI-1067) after an acute coronary syndrome: A randomised, doubleblind, placebo-controlled trial. Lancet. 2008;**371**(9626):1761-1768

[193] Rosenson RS. Phospholipase A2 inhibition and atherosclerotic vascular disease: Prospects for targeting secretory and lipoproteinassociated phospholipase A2 enzymes. Current Opinion in Lipidology. 2010;**21**(6):473-480

[194] Riccioni G, Zanasi A, Vitulano N, et al. Leukotrienes in atherosclerosis: New target inisights and future therapy perspectives. Mediators of Inflammation. 2009;**2009**:737282

[195] Lin J, Kakkar V, Lu X. Impact of MCP-1 in atherosclerosis. Current Pharmaceutical Design. 2014;**20**(28):4580-4588

[196] Tousoulis D, Oikonomou E, Economou EK, et al. Inflammatory cytokines in atherosclerosis: Current therapeutic approaches. European Heart Journal. 2016;**37**:1723-1735

**43**

Section 2

Dyslipidemia in Special

Populations

Section 2