Atherosclerosis: Difference between revisions

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''Ronak Delewi, MD; Hayang Yang, MsC; John Kastelein, MD, PhD''<br />
''Ronak Delewi, MD; Hayang Yang, MsC; John Kastelein, MD, PhD''<br />


''A 53 years old man, without medical history or drug use, shows up in the family physician’s room and makes an anxious impression. His friend has recently suffered from myocardial infarction (MI) and he is worried that he might also face the same situation soon. As for family medical history, he has a father with hypertension and an uncle with diabetes mellitus. He doesn’t seem to have any symptoms or complaints at this moment, but he has been smoking for 25 years and is overweight. Due to these characteristics he is worried of having a high risk of getting a MI. During the physical examination, his BMI was 29, RR was 152/90 mmHg and heart rate was 75 bpm. The family physician orders a blood test for lipid profile and glucose. Both turn out to be in the normal range. <br />
:''A 53 years old man, without medical history or drug use, shows up in the family physician’s room and makes an anxious impression. His friend has recently suffered from myocardial infarction (MI) and he is worried that he might also face the same situation soon. As for family medical history, he has a father with hypertension and an uncle with diabetes mellitus. He doesn’t seem to have any symptoms or complaints at this moment, but he has been smoking for 25 years and is overweight. Due to these characteristics he is worried of having a high risk of getting a MI. During the physical examination, his BMI was 29, RR was 152/90 mmHg and heart rate was 75 bpm. The family physician orders a blood test for lipid profile and glucose. Both turn out to be in the normal range. ''<br />


The family physician gives the patient several advices concerning primary prevention for atherosclerosis; quit smoking, try to achieve weight reduction, do regular physical activity, restrict alcohol consumption to <10-30g/day and follow a varied and balanced diet. Regarding the hypertension, the advice is to keep his RR under 140/90 mmHg. Antihypertensive medication is not indicated at this moment, because his 10-years risk of death due to cardiovascular diseases (Systematic COronary Risk Evaluation) is lower than 20%. He is advised for regular checkups of cardiovascular risk profile or report to the doctor’s office in case of chest pain.''<br />
:''The family physician gives the patient several advices concerning primary prevention for atherosclerosis; quit smoking, try to achieve weight reduction, do regular physical activity, restrict alcohol consumption to <10-30g/day and follow a varied and balanced diet. Regarding the hypertension, the advice is to keep his RR under 140/90 mmHg. Antihypertensive medication is not indicated at this moment, because his 10-years risk of death due to cardiovascular diseases (Systematic COronary Risk Evaluation) is lower than 20%. He is advised for regular checkups of cardiovascular risk profile or report to the doctor’s office in case of chest pain.''<br />


== History ==
== History ==
Since the 20th century, cardiovascular diseases (CVD’s) have grown to be the leading cause of death and disability in the world, illustrated by 17.3 million deaths per year in 2008. Out of all cardiovascular diseases, coronary heart disease (46% among males, 38% among females) and cerebrovascular disease (34% among males, 37% among females) are accountable for the largest proportion of CVDs. In 2008, heart attack and stroke were responsible for 7.3 million deaths and 6.2 million deaths subsequently. Obstructive coronary and cerebrovascular disease are caused in most instances by atherosclerosis. It is a life-time illness that over time can eventually lead to obstructive disease. Once atherosclerotic lesions become clinically significant, serious acute complications such as ischemic heart disease, MI and stroke may occur. This chapter concerns the complex pathological process of atherosclerosis, possible consequences of atherosclerosis and the most recent treatment for atherosclerosis in order to prevent CVD’s. <br />
:Since the 20th century, cardiovascular diseases (CVD’s) have grown to be the leading cause of death and disability in the world, illustrated by 17.3 million deaths per year in 2008. Out of all cardiovascular diseases, coronary heart disease (46% among males, 38% among females) and cerebrovascular disease (34% among males, 37% among females) are accountable for the largest proportion of CVDs. In 2008, heart attack and stroke were responsible for 7.3 million deaths and 6.2 million deaths subsequently. Obstructive coronary and cerebrovascular disease are caused in most instances by atherosclerosis. It is a life-time illness that over time can eventually lead to obstructive disease. Once atherosclerotic lesions become clinically significant, serious acute complications such as ischemic heart disease, MI and stroke may occur. This chapter concerns the complex pathological process of atherosclerosis, possible consequences of atherosclerosis and the most recent treatment for atherosclerosis in order to prevent CVD’s. <br />


== 1.1 Arterial vessel in homeostasis ==
== 1.1 Arterial vessel in homeostasis ==
The core of the pathogenesis of atherosclerosis is dysfunction of arterial vessels. In order to understand the pathogenesis of atherosclerosis, it is thus necessary to know about the functions and state of non-pathological arterial vessels.<br />
:The core of the pathogenesis of atherosclerosis is dysfunction of arterial vessels. In order to understand the pathogenesis of atherosclerosis, it is thus necessary to know about the functions and state of non-pathological arterial vessels.<br />


=== Three layers of arterial vessel ===
=== Three layers of arterial vessel ===
The normal arterial vessel consists of 3 layers, namely intima, media and outer adventitia.<br />
:The normal arterial vessel consists of 3 layers, namely intima, media and outer adventitia.<br />
The intima is located closest to the arterial lumen and is therefore most ‘intimate’ with the blood. This layer is composed of a single layer of endothelial cells (endothelium), connective tissue, and several smooth muscle cells. The endothelium functions as an active metabolic barrier as well as a carrier between blood and the arterial wall. It plays a crucial role in atherosclerosis. Connective tissue consists of a matrix of collagen, proteoglycans and elastin. Lymphocytes, macrophages and other types of inflammatory cells may occasionally reside in the intima. <br />


The media is the middle layer and is bounded by the internal and external elastic laminae. The media consists of layers of smooth muscle cells with contractile and synthetic function. As for the contractile function, smooth muscle cells enable vasoconstriction and vasodilatation. As for the synthetic function, they are responsible for the growth of the vascular extracellular matrix.<br />
:The intima is located closest to the arterial lumen and is therefore most ‘intimate’ with the blood. This layer is composed of a single layer of endothelial cells (endothelium), connective tissue, and several smooth muscle cells. The endothelium functions as an active metabolic barrier as well as a carrier between blood and the arterial wall. It plays a crucial role in atherosclerosis. Connective tissue consists of a matrix of collagen, proteoglycans and elastin. Lymphocytes, macrophages and other types of inflammatory cells may occasionally reside in the intima. <br />


The most external vessel wall layer is called the adventitia and contains fibroblasts, connective tissue, nerves, lymphatics and vasa vasorum. Inflammatory cells may occasionally reside in the adventitia. <br />
:The media is the middle layer and is bounded by the internal and external elastic laminae. The media consists of layers of smooth muscle cells with contractile and synthetic function. As for the contractile function, smooth muscle cells enable vasoconstriction and vasodilatation. As for the synthetic function, they are responsible for the growth of the vascular extracellular matrix.<br />


There is a constant dynamic interchange between the arterial wall and its cellular components and the surrounding extracellular matrix. By learning the physiology of this dynamic interchange and the functions of each cellular component, the dysfunction of these cellular components leading to atherogenesis can be understood. <br />
:The most external vessel wall layer is called the adventitia and contains fibroblasts, connective tissue, nerves, lymphatics and vasa vasorum. Inflammatory cells may occasionally reside in the adventitia. <br />
 
:There is a constant dynamic interchange between the arterial wall and its cellular components and the surrounding extracellular matrix. By learning the physiology of this dynamic interchange and the functions of each cellular component, the dysfunction of these cellular components leading to atherogenesis can be understood. <br />


=== Cellular components involved in atherosclerosis ===
=== Cellular components involved in atherosclerosis ===
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