Lecturio Medical Knowledge Essentials – Atherosclerosis

Authors: Ahmed Elsherif ¹ ; Michelle Wyatt ²
Peer Reviewers: Stanley Oiseth ³ ; Joseph Alpert ⁴
Affiliations: ¹ Suez Canal University; ² Medical Editor at Lecturio; ³ Chief Medical Editor at Lecturio; ⁴ Tucson University, Arizona

This article is not intended to substitute for professional medical advice and should not be relied on as health or personal advice. Always seek the guidance of your doctor or other qualified health professional with any questions you may have regarding your health or a medical condition.

Definition

Atherosclerosis Atherosclerosis Atherosclerosis is a common form of arterial disease in which lipid deposition forms a plaque in the blood vessel walls. Atherosclerosis is an incurable disease, for which there are clearly defined risk factors that often can be reduced through a change in lifestyle and behavior of the patient. Atherosclerosis is the thickening of the arterial wall and loss of elasticity Elasticity Resistance and recovery from distortion of shape. Skeletal Muscle Contraction due to variable Variable Variables represent information about something that can change. The design of the measurement scales, or of the methods for obtaining information, will determine the data gathered and the characteristics of that data. As a result, a variable can be qualitative or quantitative, and may be further classified into subgroups. Types of Variables pathogenesis. The term atherosclerosis Atherosclerosis Atherosclerosis is a common form of arterial disease in which lipid deposition forms a plaque in the blood vessel walls. Atherosclerosis is an incurable disease, for which there are clearly defined risk factors that often can be reduced through a change in lifestyle and behavior of the patient. Atherosclerosis is derived from the Greek words “athērē” meaning a substance like hulled grain kernels or porridge, plus “sklērōsis” meaning hardening. The changes in atherosclerosis Atherosclerosis Atherosclerosis is a common form of arterial disease in which lipid deposition forms a plaque in the blood vessel walls. Atherosclerosis is an incurable disease, for which there are clearly defined risk factors that often can be reduced through a change in lifestyle and behavior of the patient. Atherosclerosis occur in the intima and media of blood vessel walls and lead to stiffening the vessel walls and narrowing the vascular lumen.[1]

Epidemiology

Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of death worldwide. Within the USA and EU, atherosclerosis Atherosclerosis Atherosclerosis is a common form of arterial disease in which lipid deposition forms a plaque in the blood vessel walls. Atherosclerosis is an incurable disease, for which there are clearly defined risk factors that often can be reduced through a change in lifestyle and behavior of the patient. Atherosclerosis involving the coronary, cerebral, and peripheral arteries Arteries Arteries are tubular collections of cells that transport oxygenated blood and nutrients from the heart to the tissues of the body. The blood passes through the arteries in order of decreasing luminal diameter, starting in the largest artery (the aorta) and ending in the small arterioles. Arteries are classified into 3 types: large elastic arteries, medium muscular arteries, and small arteries and arterioles. Arteries: Histology accounts for more morbidity Morbidity The proportion of patients with a particular disease during a given year per given unit of population. Measures of Health Status and mortality Mortality All deaths reported in a given population. Measures of Health Status than any other disease (approximately 50% of all deaths), with many deaths occurring under age 65.[2,3]

Etiology

Atherosclerosis Atherosclerosis Atherosclerosis is a common form of arterial disease in which lipid deposition forms a plaque in the blood vessel walls. Atherosclerosis is an incurable disease, for which there are clearly defined risk factors that often can be reduced through a change in lifestyle and behavior of the patient. Atherosclerosis is a chronic inflammatory disorder that occurs in the walls of blood vessels. Oxidized low-density lipoprotein Low-density lipoprotein A class of lipoproteins of small size (18-25 nm) and light (1. 019-1. 063 g/ml) particles with a core composed mainly of cholesterol esters and smaller amounts of triglycerides. The surface monolayer consists mostly of phospholipids, a single copy of apolipoprotein B-100, and free cholesterol molecules. The main ldl function is to transport cholesterol and cholesterol esters to extrahepatic tissues. Cholesterol Metabolism (LDL) cholesterol Cholesterol The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. Cholesterol Metabolism is involved in the inflammatory process.[4] Lipids Lipids Lipids are a diverse group of hydrophobic organic molecules, which include fats, oils, sterols, and waxes. Fatty Acids and Lipids, calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes, and other cellular debris are stored in the intima of large and medium-sized arteries Medium-Sized Arteries Kawasaki Disease, thereby causing the inflammatory process to cause vessel wall thickening and plaque Plaque Primary Skin Lesions formation.

Hyperlipidemia, especially hypercholesterolemia Hypercholesterolemia A condition with abnormally high levels of cholesterol in the blood. It is defined as a cholesterol value exceeding the 95th percentile for the population. Lipid Disorders, is a significant risk factor for atherosclerosis Atherosclerosis Atherosclerosis is a common form of arterial disease in which lipid deposition forms a plaque in the blood vessel walls. Atherosclerosis is an incurable disease, for which there are clearly defined risk factors that often can be reduced through a change in lifestyle and behavior of the patient. Atherosclerosis. LDL cholesterol Cholesterol The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. Cholesterol Metabolism (“bad cholesterol Cholesterol The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. Cholesterol Metabolism”) is the primary culprit in the clogging of arteries Arteries Arteries are tubular collections of cells that transport oxygenated blood and nutrients from the heart to the tissues of the body. The blood passes through the arteries in order of decreasing luminal diameter, starting in the largest artery (the aorta) and ending in the small arterioles. Arteries are classified into 3 types: large elastic arteries, medium muscular arteries, and small arteries and arterioles. Arteries: Histology. The lipid-cholesterol-protein complex delivers cholesterol Cholesterol The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. Cholesterol Metabolism to peripheral tissues; at the same time, high-density lipoprotein High-density lipoprotein A class of lipoproteins of small size (4-13 nm) and dense (greater than 1. 063 g/ml) particles. HDL lipoproteins, synthesized in the liver without a lipid core, accumulate cholesterol esters from peripheral tissues and transport them to the liver for re-utilization or elimination from the body (the reverse cholesterol transport). Their major protein component is apolipoprotein A-I. HDL also shuttle apolipoproteins C and apolipoproteins E to and from triglyceride-rich lipoproteins during their catabolism. Hdl plasma level has been inversely correlated with the risk of cardiovascular diseases. Cholesterol Metabolism (HDL) mobilizes cholesterol Cholesterol The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. Cholesterol Metabolism from the periphery (even from atheromas) and transports it to the liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy for catabolism and biliary excretion. High HDL (“good cholesterol Cholesterol The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. Cholesterol Metabolism”) levels are associated with reduced risk of atherosclerosis Atherosclerosis Atherosclerosis is a common form of arterial disease in which lipid deposition forms a plaque in the blood vessel walls. Atherosclerosis is an incurable disease, for which there are clearly defined risk factors that often can be reduced through a change in lifestyle and behavior of the patient. Atherosclerosis; low levels correlate with higher risk. Hypercholesterolemia Hypercholesterolemia A condition with abnormally high levels of cholesterol in the blood. It is defined as a cholesterol value exceeding the 95th percentile for the population. Lipid Disorders can be caused by abetalipoproteinemia, lipoprotein lipase Lipase An enzyme of the hydrolase class that catalyzes the reaction of triacylglycerol and water to yield diacylglycerol and a fatty acid anion. It is produced by glands on the tongue and by the pancreas and initiates the digestion of dietary fats. Malabsorption and Maldigestion, apolipoprotein C-II deficiencies, and familial dysbetalipoproteinemia.[5]

Risk Factors

The risk factors associated with the development of atherosclerosis Atherosclerosis Atherosclerosis is a common form of arterial disease in which lipid deposition forms a plaque in the blood vessel walls. Atherosclerosis is an incurable disease, for which there are clearly defined risk factors that often can be reduced through a change in lifestyle and behavior of the patient. Atherosclerosis are divided into modifiable and nonmodifiable risk factors. Nonmodifiable risk factors are male sex Sex The totality of characteristics of reproductive structure, functions, phenotype, and genotype, differentiating the male from the female organism. Gender Dysphoria, age, genetic abnormalities, and family history Family History Adult Health Maintenance. The modifiable risk factors include hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension, hyperlipidemia, cigarette smoking Smoking Willful or deliberate act of inhaling and exhaling smoke from burning substances or agents held by hand. Interstitial Lung Diseases, and diabetes Diabetes Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus.[6,31] The modifiable factors can be subdivided into first and second-order risk factors.

First-Order Modifiable Risk Factors

• Cigarette smoking Smoking Willful or deliberate act of inhaling and exhaling smoke from burning substances or agents held by hand. Interstitial Lung Diseases promotes early development and rapid progression of atherosclerosis Atherosclerosis Atherosclerosis is a common form of arterial disease in which lipid deposition forms a plaque in the blood vessel walls. Atherosclerosis is an incurable disease, for which there are clearly defined risk factors that often can be reduced through a change in lifestyle and behavior of the patient. Atherosclerosis.
• Arterial hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension: Due to the high-pressure load, endothelial damage occurs faster.
• Diabetes Diabetes Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus mellitus: Increased blood glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance levels cause reactive glycosylation Glycosylation The chemical or biochemical addition of carbohydrate or glycosyl groups to other chemicals, especially peptides or proteins. Glycosyl transferases are used in this biochemical reaction. Post-translational Protein Processing, causing increased phagocytosis Phagocytosis The engulfing and degradation of microorganisms; other cells that are dead, dying, or pathogenic; and foreign particles by phagocytic cells (phagocytes). Innate Immunity: Phagocytes and Antigen Presentation and endothelial damage.
• Hyperlipidemia: Excessive LDL cholesterol Cholesterol The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. Cholesterol Metabolism increases the risk of atherosclerosis Atherosclerosis Atherosclerosis is a common form of arterial disease in which lipid deposition forms a plaque in the blood vessel walls. Atherosclerosis is an incurable disease, for which there are clearly defined risk factors that often can be reduced through a change in lifestyle and behavior of the patient. Atherosclerosis, especially if HDL cholesterol Cholesterol The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. Cholesterol Metabolism levels are also low.

Second-Order Modifiable Risk Factors

• Lack of exercise 
• Psychological or emotional stress 
• Obesity Obesity Obesity is a condition associated with excess body weight, specifically with the deposition of excessive adipose tissue. Obesity is considered a global epidemic. Major influences come from the western diet and sedentary lifestyles, but the exact mechanisms likely include a mixture of genetic and environmental factors. Obesity 
• Hyperuricemia Hyperuricemia Excessive uric acid or urate in blood as defined by its solubility in plasma at 37 degrees c; greater than 0. 42 mmol per liter (7. 0 mg/dl) in men or 0. 36 mmol per liter (6. 0 mg/dl) in women. Gout 
• Hypertriglyceridemia Hypertriglyceridemia A condition of elevated levels of triglycerides in the blood. Lipid Disorders 
• Hyperglycemia Hyperglycemia Abnormally high blood glucose level. Diabetes Mellitus and diabetes Diabetes Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus mellitus
• Increased lipoprotein (a)

Classification

There are four types of arteriosclerosis, the general term for “hardening of the arteries Arteries Arteries are tubular collections of cells that transport oxygenated blood and nutrients from the heart to the tissues of the body. The blood passes through the arteries in order of decreasing luminal diameter, starting in the largest artery (the aorta) and ending in the small arterioles. Arteries are classified into 3 types: large elastic arteries, medium muscular arteries, and small arteries and arterioles. Arteries: Histology.” Macroangiopathy refers to changes in large and medium-sized arteries Medium-Sized Arteries Kawasaki Disease. In contrast, in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension, microangiopathy refers to the pathologic changes in the arterioles Arterioles The smallest divisions of the arteries located between the muscular arteries and the capillaries. Arteries: Histology, also called arteriolosclerosis. 

The four types of arteriosclerosis are atherosclerosis Atherosclerosis Atherosclerosis is a common form of arterial disease in which lipid deposition forms a plaque in the blood vessel walls. Atherosclerosis is an incurable disease, for which there are clearly defined risk factors that often can be reduced through a change in lifestyle and behavior of the patient. Atherosclerosis (the most common), arteriolosclerosis, Mönckeberg medial sclerosis Sclerosis A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. Wilms Tumor (characterized by calcifications of the medial walls of muscular arteries Arteries Arteries are tubular collections of cells that transport oxygenated blood and nutrients from the heart to the tissues of the body. The blood passes through the arteries in order of decreasing luminal diameter, starting in the largest artery (the aorta) and ending in the small arterioles. Arteries are classified into 3 types: large elastic arteries, medium muscular arteries, and small arteries and arterioles. Arteries: Histology), and fibromuscular intimal hyperplasia Hyperplasia An increase in the number of cells in a tissue or organ without tumor formation. It differs from hypertrophy, which is an increase in bulk without an increase in the number of cells. Cellular Adaptation (in muscular arteries Arteries Arteries are tubular collections of cells that transport oxygenated blood and nutrients from the heart to the tissues of the body. The blood passes through the arteries in order of decreasing luminal diameter, starting in the largest artery (the aorta) and ending in the small arterioles. Arteries are classified into 3 types: large elastic arteries, medium muscular arteries, and small arteries and arterioles. Arteries: Histology larger than arterioles Arterioles The smallest divisions of the arteries located between the muscular arteries and the capillaries. Arteries: Histology, caused by inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body's defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation or injury)

Hyaline arteriolosclerosis, in response to hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension, shows homogeneous Homogeneous Imaging of the Spleen, pink hyaline thickening of the arterioles Arterioles The smallest divisions of the arteries located between the muscular arteries and the capillaries. Arteries: Histology due to plasma Plasma The residual portion of blood that is left after removal of blood cells by centrifugation without prior blood coagulation. Transfusion Products protein leakage across injured endothelial cells and increased smooth muscle cells (SMCs). This results in luminal narrowing and is more severe in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with diabetes Diabetes Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus. Hyperplastic Hyperplastic Colon Polyps arteriolosclerosis occurs in severe cases of hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension; the arterioles Arterioles The smallest divisions of the arteries located between the muscular arteries and the capillaries. Arteries: Histology show concentric, laminated (“onion-skin”) thickening of the walls due to SMC proliferation and thickened, reduplicated basement membranes. In patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with severe or malignant hypertension Malignant Hypertension Hypertensive Retinopathy, fibrinoid deposits and vessel wall necrosis Necrosis The death of cells in an organ or tissue due to disease, injury or failure of the blood supply. Ischemic Cell Damage (necrotizing arteriolitis) are seen most notably in the kidney.

The Various Degrees of Severity of Atherosclerosis Atherosclerosis Atherosclerosis is a common form of arterial disease in which lipid deposition forms a plaque in the blood vessel walls. Atherosclerosis is an incurable disease, for which there are clearly defined risk factors that often can be reduced through a change in lifestyle and behavior of the patient. Atherosclerosis

Mild	Moderate	Severe
Endothelium Endothelium A layer of epithelium that lines the heart, blood vessels (vascular endothelium), lymph vessels (lymphatic endothelium), and the serous cavities of the body. Arteries: Histology becomes damaged. Factors: hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension, smoking Smoking Willful or deliberate act of inhaling and exhaling smoke from burning substances or agents held by hand. Interstitial Lung Diseases	Damage causes an inflammatory response and WBCs deposit cholesterol Cholesterol The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. Cholesterol Metabolism, forming an atheroma. Calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes and fibrous Fibrous Fibrocystic Change tissue form a plaque Plaque Primary Skin Lesions. Artery loses elasticity Elasticity Resistance and recovery from distortion of shape. Skeletal Muscle Contraction and narrows.	Plaque Plaque Primary Skin Lesions restricts blood flow Blood flow Blood flow refers to the movement of a certain volume of blood through the vasculature over a given unit of time (e.g., mL per minute). Vascular Resistance, Flow, and Mean Arterial Pressure and increases blood pressure. Increased blood pressure promotes the formation of more plaque Plaque Primary Skin Lesions.

Clinical Features

Atherosclerosis Atherosclerosis Atherosclerosis is a common form of arterial disease in which lipid deposition forms a plaque in the blood vessel walls. Atherosclerosis is an incurable disease, for which there are clearly defined risk factors that often can be reduced through a change in lifestyle and behavior of the patient. Atherosclerosis can be present for years and decades without any symptoms. Common manifestations include coronary artery Coronary Artery Truncus Arteriosus disease, cerebrovascular disease, peripheral artery disease Peripheral artery disease Peripheral artery disease (PAD) is obstruction of the arterial lumen resulting in decreased blood flow to the distal limbs. The disease can be a result of atherosclerosis or thrombosis. Patients may be asymptomatic or have progressive claudication, skin discoloration, ischemic ulcers, or gangrene. Peripheral Artery Disease, and abdominal aortic aneurysm Aortic aneurysm An abnormal balloon- or sac-like dilatation in the wall of aorta. Thoracic Aortic Aneurysms.

High-yield fact:

Metabolic syndrome Metabolic syndrome Metabolic syndrome is a cluster of conditions that significantly increases the risk for several secondary diseases, notably cardiovascular disease, type 2 diabetes, and nonalcoholic fatty liver. In general, it is agreed that hypertension, insulin resistance/hyperglycemia, and hyperlipidemia, along with central obesity, are components of the metabolic syndrome. Metabolic Syndrome refers to the presence of at least 3 of these 5 risk factors: [7] 

• Abdominal obesity Abdominal obesity A condition of having excess fat in the abdomen. Abdominal obesity is typically defined as waist circumferences of 40 inches or more in men and 35 inches or more in women. Abdominal obesity raises the risk of developing disorders, such as diabetes; hypertension; and metabolic syndrome. Obesity ( waist circumference Waist circumference Measure of abdominal obesity and is associated with increased cardiovascular risks. Obesity > 102 cm (40 inches) in men,  > 88 cm (35 inches) in women).
• Triglycerides Triglycerides Fatty Acids and Lipids ≥ 150 mg/dL or drug treatment for elevated triglycerides Triglycerides Fatty Acids and Lipids
• HDL cholesterol Cholesterol The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. Cholesterol Metabolism < 40 mg/dL in men or < 50 mg/dL in women, or drug treatment for low HDL cholesterol Cholesterol The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. Cholesterol Metabolism
• Fasting plasma Plasma The residual portion of blood that is left after removal of blood cells by centrifugation without prior blood coagulation. Transfusion Products glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance > 100 mg/dL or drug treatment for elevated blood glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance 
• Blood pressure > 130/85 mm Hg or drug treatment for hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension

Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with metabolic syndrome Metabolic syndrome Metabolic syndrome is a cluster of conditions that significantly increases the risk for several secondary diseases, notably cardiovascular disease, type 2 diabetes, and nonalcoholic fatty liver. In general, it is agreed that hypertension, insulin resistance/hyperglycemia, and hyperlipidemia, along with central obesity, are components of the metabolic syndrome. Metabolic Syndrome and an elevated albumin-to-creatinine ratio or elevated serum aspartate Aspartate One of the non-essential amino acids commonly occurring in the l-form. It is found in animals and plants, especially in sugar cane and sugar beets. It may be a neurotransmitter. Synthesis of Nonessential Amino Acids aminotransferase ( AST AST Enzymes of the transferase class that catalyze the conversion of l-aspartate and 2-ketoglutarate to oxaloacetate and l-glutamate. Liver Function Tests) and alanine Alanine A non-essential amino acid that occurs in high levels in its free state in plasma. It is produced from pyruvate by transamination. It is involved in sugar and acid metabolism, increases immunity, and provides energy for muscle tissue, brain, and the central nervous system. Synthesis of Nonessential Amino Acids aminotransferase ( ALT ALT An enzyme that catalyzes the conversion of l-alanine and 2-oxoglutarate to pyruvate and l-glutamate. Liver Function Tests) have an elevated risk of CHD mortality Mortality All deaths reported in a given population. Measures of Health Status. [8]

Pathophysiology

The current theory of pathogenesis is called the “response to injury” hypothesis Hypothesis A hypothesis is a preliminary answer to a research question (i.e., a “guess” about what the results will be). There are 2 types of hypotheses: the null hypothesis and the alternative hypothesis. Statistical Tests and Data Representation. The endothelium Endothelium A layer of epithelium that lines the heart, blood vessels (vascular endothelium), lymph vessels (lymphatic endothelium), and the serous cavities of the body. Arteries: Histology is injured first, inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body's defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation occurs, and atherosclerosis Atherosclerosis Atherosclerosis is a common form of arterial disease in which lipid deposition forms a plaque in the blood vessel walls. Atherosclerosis is an incurable disease, for which there are clearly defined risk factors that often can be reduced through a change in lifestyle and behavior of the patient. Atherosclerosis results from chronic inflammatory and healing responses of the arterial wall.[9] Early and evolving changes involve the progression of a complex interaction of modified lipoproteins Lipoproteins Lipid-protein complexes involved in the transportation and metabolism of lipids in the body. They are spherical particles consisting of a hydrophobic core of triglycerides and cholesterol esters surrounded by a layer of hydrophilic free cholesterol; phospholipids; and apolipoproteins. Lipoproteins are classified by their varying buoyant density and sizes. Lipid Metabolism, macrophages Macrophages The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood monocytes. Main types are peritoneal macrophages; alveolar macrophages; histiocytes; kupffer cells of the liver; and osteoclasts. They may further differentiate within chronic inflammatory lesions to epithelioid cells or may fuse to form foreign body giant cells or langhans giant cells. Innate Immunity: Phagocytes and Antigen Presentation, and T lymphocytes T lymphocytes Lymphocytes responsible for cell-mediated immunity. Two types have been identified - cytotoxic (t-lymphocytes, cytotoxic) and helper T-lymphocytes (t-lymphocytes, helper-inducer). They are formed when lymphocytes circulate through the thymus gland and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen. T cells: Types and Functions with endothelial cells (ECs) and smooth muscle cells (SMCs) of the arterial wall. In summary, atherosclerosis Atherosclerosis Atherosclerosis is a common form of arterial disease in which lipid deposition forms a plaque in the blood vessel walls. Atherosclerosis is an incurable disease, for which there are clearly defined risk factors that often can be reduced through a change in lifestyle and behavior of the patient. Atherosclerosis progresses in the following sequence [4]: 

• Endothelial injury and dysfunction, increased vascular permeability; leukocyte adhesion Leukocyte adhesion Leukocyte Adhesion Deficiency Type 1 and thrombosis Thrombosis Formation and development of a thrombus or blood clot in the blood vessel. Epidemic Typhus
• Disruption of nitric oxide Nitric Oxide A free radical gas produced endogenously by a variety of mammalian cells, synthesized from arginine by nitric oxide synthase. Nitric oxide is one of the endothelium-dependent relaxing factors released by the vascular endothelium and mediates vasodilation. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic guanylate cyclase and thus elevates intracellular levels of cyclic gmp. Pulmonary Hypertension Drugs (NO) synthesis Synthesis Polymerase Chain Reaction (PCR); endothelial dysfunction occurs due  to the endothelial injury
• Accumulation of lipoproteins Lipoproteins Lipid-protein complexes involved in the transportation and metabolism of lipids in the body. They are spherical particles consisting of a hydrophobic core of triglycerides and cholesterol esters surrounded by a layer of hydrophilic free cholesterol; phospholipids; and apolipoproteins. Lipoproteins are classified by their varying buoyant density and sizes. Lipid Metabolism (mainly LDL and its oxidized forms) in the vessel wall
• Adherence of monocytes Monocytes Large, phagocytic mononuclear leukocytes produced in the vertebrate bone marrow and released into the blood; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles. Innate Immunity: Phagocytes and Antigen Presentation to the endothelium Endothelium A layer of epithelium that lines the heart, blood vessels (vascular endothelium), lymph vessels (lymphatic endothelium), and the serous cavities of the body. Arteries: Histology; migration into the intima and transformation Transformation Change brought about to an organism's genetic composition by unidirectional transfer (transfection; transduction, genetic; conjugation, genetic, etc.) and incorporation of foreign DNA into prokaryotic or eukaryotic cells by recombination of part or all of that DNA into the cell's genome. Bacteriology into macrophages Macrophages The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood monocytes. Main types are peritoneal macrophages; alveolar macrophages; histiocytes; kupffer cells of the liver; and osteoclasts. They may further differentiate within chronic inflammatory lesions to epithelioid cells or may fuse to form foreign body giant cells or langhans giant cells. Innate Immunity: Phagocytes and Antigen Presentation and foam cells Foam cells Lipid-laden macrophages originating from monocytes or from smooth muscle cells. Atherosclerosis (containing lipid vacuoles)
• Platelet adhesion Adhesion The process whereby platelets adhere to something other than platelets, e.g., collagen; basement membrane; microfibrils; or other 'foreign' surfaces. Coagulation Studies
• Factor release from activated platelets Platelets Platelets are small cell fragments involved in hemostasis. Thrombopoiesis takes place primarily in the bone marrow through a series of cell differentiation and is influenced by several cytokines. Platelets are formed after fragmentation of the megakaryocyte cytoplasm. Platelets: Histology, macrophages Macrophages The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood monocytes. Main types are peritoneal macrophages; alveolar macrophages; histiocytes; kupffer cells of the liver; and osteoclasts. They may further differentiate within chronic inflammatory lesions to epithelioid cells or may fuse to form foreign body giant cells or langhans giant cells. Innate Immunity: Phagocytes and Antigen Presentation, and endothelial cells; SMC recruitment Recruitment Skeletal Muscle Contraction.
• SMC proliferation, extracellular matrix Extracellular matrix A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere. Hypertrophic and Keloid Scars (ECM) production, and T cell recruitment Recruitment Skeletal Muscle Contraction
• Lipid accumulation both extracellularly and within cells ( macrophages Macrophages The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood monocytes. Main types are peritoneal macrophages; alveolar macrophages; histiocytes; kupffer cells of the liver; and osteoclasts. They may further differentiate within chronic inflammatory lesions to epithelioid cells or may fuse to form foreign body giant cells or langhans giant cells. Innate Immunity: Phagocytes and Antigen Presentation and SMCs)
• Calcification of ECM and necrotic debris (late in the pathogenesis)

Initially, LDL cholesterol Cholesterol The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. Cholesterol Metabolism is deposited in the intima of the vessel wall. It is then oxidized and is followed by a local inflammatory response, i.e., monocytes Monocytes Large, phagocytic mononuclear leukocytes produced in the vertebrate bone marrow and released into the blood; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles. Innate Immunity: Phagocytes and Antigen Presentation start migrating into the tissue. After they phagocytize the LDL cholesterol Cholesterol The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. Cholesterol Metabolism, foam cells Foam cells Lipid-laden macrophages originating from monocytes or from smooth muscle cells. Atherosclerosis containing lipid vacuoles are formed. These early atherosclerotic lesions are called fatty streaks Fatty streaks Atherosclerosis and occur especially in areas with high mechanical stress (for example, at the proximal left anterior descending artery (LAD) and the carotid bifurcation).

Gradually, there is an accumulation of lipids Lipids Lipids are a diverse group of hydrophobic organic molecules, which include fats, oils, sterols, and waxes. Fatty Acids and Lipids and cellular debris in the intima. Different cells within the vessel walls release mediators, and muscle cells from the tunica media Tunica media The middle layer of blood vessel walls, composed principally of thin, cylindrical, smooth muscle cells and elastic tissue. It accounts for the bulk of the wall of most arteries. The smooth muscle cells are arranged in circular layers around the vessel, and the thickness of the coat varies with the size of the vessel. Arteries: Histology migrate into the intima and proliferate.

The fatty core is surrounded by connective tissue Connective tissue Connective tissues originate from embryonic mesenchyme and are present throughout the body except inside the brain and spinal cord. The main function of connective tissues is to provide structural support to organs. Connective tissues consist of cells and an extracellular matrix. Connective Tissue: Histology, making it dense and inaccessible; hence, the stored LDL cholesterol Cholesterol The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. Cholesterol Metabolism cannot be degraded. These plaques may contain newly-formed vessels (originating from the vasa vasorum Vasa vasorum Nutrient blood vessels which supply the walls of large arteries or veins. Arteries: Histology) that can bleed into the plaque Plaque Primary Skin Lesions. Calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes starts to accumulate in the growing plaque Plaque Primary Skin Lesions. 

Plaques with a sizeable lipid core and only a thin fibrous Fibrous Fibrocystic Change cap are at risk of rupture, leading to such intense activation of the coagulation system that complete thrombotic occlusion of a vessel occurs. 

Plaque Plaque Primary Skin Lesions rupture can also cause cholesterol Cholesterol The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. Cholesterol Metabolism emboli to migrate to remote blood vessels, for example, the renal arteries Arteries Arteries are tubular collections of cells that transport oxygenated blood and nutrients from the heart to the tissues of the body. The blood passes through the arteries in order of decreasing luminal diameter, starting in the largest artery (the aorta) and ending in the small arterioles. Arteries are classified into 3 types: large elastic arteries, medium muscular arteries, and small arteries and arterioles. Arteries: Histology. 

Another consequence of atherosclerosis Atherosclerosis Atherosclerosis is a common form of arterial disease in which lipid deposition forms a plaque in the blood vessel walls. Atherosclerosis is an incurable disease, for which there are clearly defined risk factors that often can be reduced through a change in lifestyle and behavior of the patient. Atherosclerosis is the formation of an aneurysm Aneurysm An aneurysm is a bulging, weakened area of a blood vessel that causes an abnormal widening of its diameter > 1.5 times the size of the native vessel. Aneurysms occur more often in arteries than in veins and are at risk of dissection and rupture, which can be life-threatening. Thoracic Aortic Aneurysms mainly caused by extracellular matrix Extracellular matrix A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere. Hypertrophic and Keloid Scars degradation and interference with the vascular supply of the tunica media Tunica media The middle layer of blood vessel walls, composed principally of thin, cylindrical, smooth muscle cells and elastic tissue. It accounts for the bulk of the wall of most arteries. The smooth muscle cells are arranged in circular layers around the vessel, and the thickness of the coat varies with the size of the vessel. Arteries: Histology.

Critical stenosis Stenosis Hypoplastic Left Heart Syndrome (HLHS) is the degree of plaque Plaque Primary Skin Lesions occlusion severe enough to cause tissue ischemia Ischemia A hypoperfusion of the blood through an organ or tissue caused by a pathologic constriction or obstruction of its blood vessels, or an absence of blood circulation. Ischemic Cell Damage, thought to be 70%–75% stenosis Stenosis Hypoplastic Left Heart Syndrome (HLHS) in coronary and most other arteries Arteries Arteries are tubular collections of cells that transport oxygenated blood and nutrients from the heart to the tissues of the body. The blood passes through the arteries in order of decreasing luminal diameter, starting in the largest artery (the aorta) and ending in the small arterioles. Arteries are classified into 3 types: large elastic arteries, medium muscular arteries, and small arteries and arterioles. Arteries: Histology.[10] At this level, the arteries Arteries Arteries are tubular collections of cells that transport oxygenated blood and nutrients from the heart to the tissues of the body. The blood passes through the arteries in order of decreasing luminal diameter, starting in the largest artery (the aorta) and ending in the small arterioles. Arteries are classified into 3 types: large elastic arteries, medium muscular arteries, and small arteries and arterioles. Arteries: Histology can not dilate sufficiently to supply enough blood when there is an increase in oxygen demand, and chest pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways may occur with exertion, as in stable angina Stable angina Persistent and reproducible chest discomfort usually precipitated by a physical exertion that dissipates upon cessation of such an activity. The symptoms are manifestations of myocardial ischemia. Stable and Unstable Angina. More severe stenosis Stenosis Hypoplastic Left Heart Syndrome (HLHS) leads to an increased imbalance between oxygen demand and supply, leading to more severe ischemic heart disease Ischemic heart disease Coronary heart disease (CHD), or ischemic heart disease, describes a situation in which an inadequate supply of blood to the myocardium exists due to a stenosis of the coronary arteries, typically from atherosclerosis. Coronary Heart Disease, including ischemic cardiomyopathy Ischemic cardiomyopathy Coronary Heart Disease and infarction.

History and Physical Examination of Atherosclerosis

A patient’s history helps identify risk factors and should include family history Family History Adult Health Maintenance. The patient should also be asked about comorbidities Comorbidities The presence of co-existing or additional diseases with reference to an initial diagnosis or with reference to the index condition that is the subject of study. Comorbidity may affect the ability of affected individuals to function and also their survival; it may be used as a prognostic indicator for length of hospital stay, cost factors, and outcome or survival. St. Louis Encephalitis Virus, medications, and walking distance tolerance Tolerance Pharmacokinetics and Pharmacodynamics. 

Physical examination provides information including skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions color, temperature, and ulcerations due to peripheral artery disease Peripheral artery disease Peripheral artery disease (PAD) is obstruction of the arterial lumen resulting in decreased blood flow to the distal limbs. The disease can be a result of atherosclerosis or thrombosis. Patients may be asymptomatic or have progressive claudication, skin discoloration, ischemic ulcers, or gangrene. Peripheral Artery Disease. Blood pressure measurement is essential. Cardiac auscultation may (or may not) give information about the presence of coronary artery Coronary Artery Truncus Arteriosus atherosclerosis Atherosclerosis Atherosclerosis is a common form of arterial disease in which lipid deposition forms a plaque in the blood vessel walls. Atherosclerosis is an incurable disease, for which there are clearly defined risk factors that often can be reduced through a change in lifestyle and behavior of the patient. Atherosclerosis. An abdominal exam may reveal a systolic bruit due to renal artery Renal artery A branch of the abdominal aorta which supplies the kidneys, adrenal glands and ureters. Glomerular Filtration stenosis Stenosis Hypoplastic Left Heart Syndrome (HLHS) or an enlarged abdominal aorta Abdominal Aorta The aorta from the diaphragm to the bifurcation into the right and left common iliac arteries. Posterior Abdominal Wall: Anatomy. ECG ECG An electrocardiogram (ECG) is a graphic representation of the electrical activity of the heart plotted against time. Adhesive electrodes are affixed to the skin surface allowing measurement of cardiac impulses from many angles. The ECG provides 3-dimensional information about the conduction system of the heart, the myocardium, and other cardiac structures. Electrocardiogram (ECG) or stress testing can be helpful if significant positives are found on history and exam. [11] 

Laboratory Tests

A lipid profile Lipid profile Lipid Disorders includes total cholesterol Cholesterol The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. Cholesterol Metabolism, LDL, HDL, and triglycerides Triglycerides Fatty Acids and Lipids in identifying patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship at risk of atherosclerosis Atherosclerosis Atherosclerosis is a common form of arterial disease in which lipid deposition forms a plaque in the blood vessel walls. Atherosclerosis is an incurable disease, for which there are clearly defined risk factors that often can be reduced through a change in lifestyle and behavior of the patient. Atherosclerosis. If myocardial infarction Myocardial infarction MI is ischemia and death of an area of myocardial tissue due to insufficient blood flow and oxygenation, usually from thrombus formation on a ruptured atherosclerotic plaque in the epicardial arteries. Clinical presentation is most commonly with chest pain, but women and patients with diabetes may have atypical symptoms. Myocardial Infarction is suspected, cardiac enzymes Enzymes Enzymes are complex protein biocatalysts that accelerate chemical reactions without being consumed by them. Due to the body's constant metabolic needs, the absence of enzymes would make life unsustainable, as reactions would occur too slowly without these molecules. Basics of Enzymes including troponin I Troponin I A troponin complex subunit that inhibits actomyosin ATPase activity thereby disrupting actin and myosin interaction. There are three troponin I subtypes: troponin i1, i2 and i3. Troponin i3 is cardiac-specific whereas troponin i1 and i2 are skeletal subtypes. Troponin i3 is a biomarker for damaged or injured cardiac myocytes and mutations in troponin i3 gene are associated with familial hypertrophic cardiomyopathy. Myocardial Infarction and CK-MB are necessary.

A lab test for inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body's defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation, highly sensitive-C-reactive protein (hs-CRP), has been established as a biomarker for atherosclerosis Atherosclerosis Atherosclerosis is a common form of arterial disease in which lipid deposition forms a plaque in the blood vessel walls. Atherosclerosis is an incurable disease, for which there are clearly defined risk factors that often can be reduced through a change in lifestyle and behavior of the patient. Atherosclerosis and may identify patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship at increased risk of cardiovascular disease.[12,13] It is elevated in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with other atherosclerotic cardiovascular disease (ASCVD) risks such as smoking Smoking Willful or deliberate act of inhaling and exhaling smoke from burning substances or agents held by hand. Interstitial Lung Diseases and diabetes Diabetes Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus mellitus. There is also a positive relationship between the elevated liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy enzyme alanine Alanine A non-essential amino acid that occurs in high levels in its free state in plasma. It is produced from pyruvate by transamination. It is involved in sugar and acid metabolism, increases immunity, and provides energy for muscle tissue, brain, and the central nervous system. Synthesis of Nonessential Amino Acids aminotransferase ( ALT ALT An enzyme that catalyzes the conversion of l-alanine and 2-oxoglutarate to pyruvate and l-glutamate. Liver Function Tests) and heart disease risk.

Fasting blood glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance and hemoglobin A1c Hemoglobin A1c Products of non-enzymatic reactions between glucose and hemoglobin a, occurring as a minor fraction of the hemoglobin components of human erythrocytes. Hemoglobin a1c is hemoglobin a with glucose covalently bound to the terminal valine of the beta chain. Glycated hemoglobin a is used as an index of the average blood sugar level over a lifetime of erythrocytes. Diabetes Mellitus ( HbA1c HbA1c Products of non-enzymatic reactions between glucose and hemoglobin a, occurring as a minor fraction of the hemoglobin components of human erythrocytes. Hemoglobin a1c is hemoglobin a with glucose covalently bound to the terminal valine of the beta chain. Glycated hemoglobin a is used as an index of the average blood sugar level over a lifetime of erythrocytes. Diabetes Mellitus) are needed to diagnose diabetes Diabetes Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus mellitus or follow-up glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance control in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with uncontrolled diabetes Diabetes Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus, a significant contributing factor to both macrovascular and microvascular disease. [14]

Other tests include:

• Complete blood count
• Comprehensive metabolic panel Comprehensive metabolic panel Primary vs Secondary Headaches (CMP) for electrolytes Electrolytes Electrolytes are mineral salts that dissolve in water and dissociate into charged particles called ions, which can be either be positively (cations) or negatively (anions) charged. Electrolytes are distributed in the extracellular and intracellular compartments in different concentrations. Electrolytes are essential for various basic life-sustaining functions. Electrolytes and renal function
• Thyroid function tests Thyroid Function Tests Blood tests used to evaluate the functioning of the thyroid gland. Ion Channel Myopathy
• Rheumatoid factor Rheumatoid factor Antibodies found in adult rheumatoid arthritis patients that are directed against gamma-chain immunoglobulins. Autoimmune Hepatitis in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with suspected rheumatoid arthritis Arthritis Acute or chronic inflammation of joints. Osteoarthritis

Diagnostic Imaging

Sonography Sonography The visualization of deep structures of the body by recording the reflections or echoes of ultrasonic pulses directed into the tissues. Use of ultrasound for imaging or diagnostic purposes employs frequencies ranging from 1. 6 to 10 megahertz. Diagnostic Procedures in Gynecology

Doppler Doppler Ultrasonography applying the doppler effect, with frequency-shifted ultrasound reflections produced by moving targets (usually red blood cells) in the bloodstream along the ultrasound axis in direct proportion to the velocity of movement of the targets, to determine both direction and velocity of blood flow. Ultrasound (Sonography) sonography Sonography The visualization of deep structures of the body by recording the reflections or echoes of ultrasonic pulses directed into the tissues. Use of ultrasound for imaging or diagnostic purposes employs frequencies ranging from 1. 6 to 10 megahertz. Diagnostic Procedures in Gynecology offers a painless, non-invasive way to view the atherosclerotic burden of blood vessels. It is used to determine the ankle-brachial index Ankle-brachial index Comparison of the blood pressure between the brachial artery and the posterior tibial artery. It is a predictor of peripheral arterial disease. Cardiovascular Examination, an indicator Indicator Methods for assessing flow through a system by injection of a known quantity of an indicator, such as a dye, radionuclide, or chilled liquid, into the system and monitoring its concentration over time at a specific point in the system. Body Fluid Compartments of the severity of peripheral vascular disease in the lower extremities. There is some concern about the variability between personnel who perform the test and, thus, its reliability Reliability Reliability refers to the reproducibility of a test or research finding. Causality, Validity, and Reliability. [15]

Color duplex sonography Sonography The visualization of deep structures of the body by recording the reflections or echoes of ultrasonic pulses directed into the tissues. Use of ultrasound for imaging or diagnostic purposes employs frequencies ranging from 1. 6 to 10 megahertz. Diagnostic Procedures in Gynecology combines two methods, allows the examination of vessel sections, and gives a color code depending on the blood flow Blood flow Blood flow refers to the movement of a certain volume of blood through the vasculature over a given unit of time (e.g., mL per minute). Vascular Resistance, Flow, and Mean Arterial Pressure. Intravascular ultrasound (IVUS) can be used to assess coronary arteries Arteries Arteries are tubular collections of cells that transport oxygenated blood and nutrients from the heart to the tissues of the body. The blood passes through the arteries in order of decreasing luminal diameter, starting in the largest artery (the aorta) and ending in the small arterioles. Arteries are classified into 3 types: large elastic arteries, medium muscular arteries, and small arteries and arterioles. Arteries: Histology and provide guidance for placing drug-eluting stents.[16]

An echocardiogram Echocardiogram Transposition of the Great Vessels is done to assess structural or functional abnormalities of the heart. It is used to estimate the ejection fraction Ejection fraction Cardiac Cycle and observe the contractility of the heart for wall motion abnormalities, two important functional parameters.[17]

Angiography Angiography Radiography of blood vessels after injection of a contrast medium. Cardiac Surgery

CT and MR MR Calculated as the ratio of the total number of people who die due to all causes over a specific time period to the total number of people in the selected population. Measures of Health Status angiography Angiography Radiography of blood vessels after injection of a contrast medium. Cardiac Surgery also offer the advantage of non-invasive diagnostics over conventional angiography Angiography Radiography of blood vessels after injection of a contrast medium. Cardiac Surgery because of the better detail provided, with 3-D reconstruction possible for precise treatment planning. CT angiography Angiography Radiography of blood vessels after injection of a contrast medium. Cardiac Surgery provides a rapid assessment, especially in emergency diagnosis, whereas MR MR Calculated as the ratio of the total number of people who die due to all causes over a specific time period to the total number of people in the selected population. Measures of Health Status angiography Angiography Radiography of blood vessels after injection of a contrast medium. Cardiac Surgery has the advantage of low radiation Radiation Emission or propagation of acoustic waves (sound), electromagnetic energy waves (such as light; radio waves; gamma rays; or x-rays), or a stream of subatomic particles (such as electrons; neutrons; protons; or alpha particles). Osteosarcoma exposure. Conventional angiography Angiography Radiography of blood vessels after injection of a contrast medium. Cardiac Surgery has the advantage of being able to perform simultaneous interventions such as stent angioplasty Angioplasty Reconstruction or repair of a blood vessel, which includes the widening of a pathological narrowing of an artery or vein by the removal of atheromatous plaque material and/or the endothelial lining as well, or by dilatation (balloon angioplasty) to compress an atheroma. Except for endarterectomy, usually these procedures are performed via catheterization as minimally invasive endovascular procedures. Cardiac Surgery.

Differential Diagnoses

Vascular Diseases Similar to Atherosclerosis Atherosclerosis Atherosclerosis is a common form of arterial disease in which lipid deposition forms a plaque in the blood vessel walls. Atherosclerosis is an incurable disease, for which there are clearly defined risk factors that often can be reduced through a change in lifestyle and behavior of the patient. Atherosclerosis

In addition to atherosclerosis Atherosclerosis Atherosclerosis is a common form of arterial disease in which lipid deposition forms a plaque in the blood vessel walls. Atherosclerosis is an incurable disease, for which there are clearly defined risk factors that often can be reduced through a change in lifestyle and behavior of the patient. Atherosclerosis, other vascular diseases cause structural wall changes and lead to arterial stenosis Stenosis Hypoplastic Left Heart Syndrome (HLHS). Inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body's defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation caused by autoimmune or infectious conditions causes 5% of stenotic vascular disease. The vascular wall thickens with inflammatory infiltrates and secondary vessel wall edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema, resulting in vasculitis Vasculitis Inflammation of any one of the blood vessels, including the arteries; veins; and rest of the vasculature system in the body. Systemic Lupus Erythematosus. Damage to the endothelium Endothelium A layer of epithelium that lines the heart, blood vessels (vascular endothelium), lymph vessels (lymphatic endothelium), and the serous cavities of the body. Arteries: Histology results in thrombosis Thrombosis Formation and development of a thrombus or blood clot in the blood vessel. Epidemic Typhus. In addition to stenosis Stenosis Hypoplastic Left Heart Syndrome (HLHS), the inflammatory process can lead to vascular wall dilation or dissection.

Other causes of arterial damage

Vasculitis Vasculitis Inflammation of any one of the blood vessels, including the arteries; veins; and rest of the vasculature system in the body. Systemic Lupus Erythematosus is caused by inflammatory WBCs in blood vessel walls with reactive damage. Loss of endothelial integrity can compromise the lumen resulting in tissue ischemia Ischemia A hypoperfusion of the blood through an organ or tissue caused by a pathologic constriction or obstruction of its blood vessels, or an absence of blood circulation. Ischemic Cell Damage and necrosis Necrosis The death of cells in an organ or tissue due to disease, injury or failure of the blood supply. Ischemic Cell Damage similar to that seen with atherosclerosis Atherosclerosis Atherosclerosis is a common form of arterial disease in which lipid deposition forms a plaque in the blood vessel walls. Atherosclerosis is an incurable disease, for which there are clearly defined risk factors that often can be reduced through a change in lifestyle and behavior of the patient. Atherosclerosis. Autoimmune causes of vasculitis Vasculitis Inflammation of any one of the blood vessels, including the arteries; veins; and rest of the vasculature system in the body. Systemic Lupus Erythematosus include granulomatosis with polyangiitis Granulomatosis with Polyangiitis A multisystemic disease of a complex genetic background. It is characterized by inflammation of the blood vessels (vasculitis) leading to damage in any number of organs. The common features include granulomatous inflammation of the respiratory tract and kidneys. Most patients have measurable autoantibodies (antineutrophil cytoplasmic antibodies) against myeloblastin. Granulomatosis with Polyangiitis, microscopic polyangiitis Microscopic polyangiitis A primary systemic vasculitis of small- and some medium-sized vessels. It is characterized by a tropism for kidneys and lungs, positive association with anti-neutrophil cytoplasmic antibodies (ANCA), and a paucity of immunoglobulin deposits in vessel walls. Vasculitides, eosinophilic granulomatosis with polyangiitis Granulomatosis with Polyangiitis A multisystemic disease of a complex genetic background. It is characterized by inflammation of the blood vessels (vasculitis) leading to damage in any number of organs. The common features include granulomatous inflammation of the respiratory tract and kidneys. Most patients have measurable autoantibodies (antineutrophil cytoplasmic antibodies) against myeloblastin. Granulomatosis with Polyangiitis (Churg-Strauss), and anti-glomerular basement membrane Basement membrane A darkly stained mat-like extracellular matrix (ecm) that separates cell layers, such as epithelium from endothelium or a layer of connective tissue. The ecm layer that supports an overlying epithelium or endothelium is called basal lamina. Basement membrane (bm) can be formed by the fusion of either two adjacent basal laminae or a basal lamina with an adjacent reticular lamina of connective tissue. Bm, composed mainly of type IV collagen; glycoprotein laminin; and proteoglycan, provides barriers as well as channels between interacting cell layers. Thin Basement Membrane Nephropathy (TBMN) autoantibody disease. [18]

Buerger disease ( thromboangiitis obliterans Thromboangiitis Obliterans A non-atherosclerotic, inflammatory thrombotic disease that commonly involves small and medium-sized arteries or veins in the extremities. It is characterized by occlusive thrombosis and fibrosis in the vascular wall leading to digital and limb ischemia and ulcerations. Thromboangiitis obliterans is highly associated with tobacco smoking. Thromboangiitis Obliterans (Buerger’s Disease)) is a nonatherosclerotic inflammatory disorder that can cause occlusive thrombus but spares the blood vessel wall.

Giant cell arteritis Giant Cell Arteritis Giant cell arteritis (GCA), also known as temporal arteritis, is a type of large-vessel vasculitis that predominantly affects the aorta and its major branches, with a predilection for the branches of the carotid (including the temporal artery). Giant cell arteritis is defined by inflammatory leukocytes in the vessel walls leading to reactive damage, ischemia, and necrosis. Giant Cell Arteritis involves large- and medium-sized arteries Medium-Sized Arteries Kawasaki Disease, specifically the cranial branches of the carotid artery such as the temporal artery, with inflammatory infiltrates causing loss of vascular smooth muscle cells and elastic Elastic Connective Tissue: Histology fibers that may cause an aneurysm Aneurysm An aneurysm is a bulging, weakened area of a blood vessel that causes an abnormal widening of its diameter > 1.5 times the size of the native vessel. Aneurysms occur more often in arteries than in veins and are at risk of dissection and rupture, which can be life-threatening. Thoracic Aortic Aneurysms.

Takayasu arteritis affects large blood vessels by lymphocytic infiltrates in the aorta Aorta The main trunk of the systemic arteries. Mediastinum and Great Vessels: Anatomy causing vascular injury by releasing the cytolytic protein perforin Perforin A calcium-dependent pore-forming protein synthesized in cytolytic lymphocytes and sequestered in secretory granules. Upon immunological reaction between a cytolytic lymphocyte and a target cell, perforin is released at the plasma membrane and polymerizes into transmembrane tubules (forming pores) which lead to death of a target cell. Lymphocytes: Histology. This inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body's defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation can lead to narrowing, occlusion, or dilation of the involved areas of the arteries Arteries Arteries are tubular collections of cells that transport oxygenated blood and nutrients from the heart to the tissues of the body. The blood passes through the arteries in order of decreasing luminal diameter, starting in the largest artery (the aorta) and ending in the small arterioles. Arteries are classified into 3 types: large elastic arteries, medium muscular arteries, and small arteries and arterioles. Arteries: Histology.

Bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology such as E. coli, S. aureus S. aureus Potentially pathogenic bacteria found in nasal membranes, skin, hair follicles, and perineum of warm-blooded animals. They may cause a wide range of infections and intoxications. Staphylococcus, and viruses Viruses Minute infectious agents whose genomes are composed of DNA or RNA, but not both. They are characterized by a lack of independent metabolism and the inability to replicate outside living host cells. Virology such as herpesviruses can also cause vessel wall inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body's defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation. 

Mechanical Damage

Mechanical damage, such as trauma to arterial vessels, can cause stenosis Stenosis Hypoplastic Left Heart Syndrome (HLHS) by secondary inflammatory changes. Malignant tumors can cause infiltrative growth in the vascular wall. Even benign Benign Fibroadenoma tumors can result in vasoconstriction Vasoconstriction The physiological narrowing of blood vessels by contraction of the vascular smooth muscle. Vascular Resistance, Flow, and Mean Arterial Pressure by external compression External Compression Blunt Chest Trauma.

Treatment

These include weight normalization combined with aerobic physical activity such as jogging, swimming, or cycling and eating a healthy diet. Smoking Smoking Willful or deliberate act of inhaling and exhaling smoke from burning substances or agents held by hand. Interstitial Lung Diseases cessation is also important, and stress reduction with active relaxation techniques such as meditation are beneficial for cardiovascular risk reduction.[20]

Non-pharmacological Treatment (lifestyle modifications)

These include weight normalization in combination with sufficient aerobic physical activity such as jogging, swimming, or cycling and eating a healthy diet. Smoking Smoking Willful or deliberate act of inhaling and exhaling smoke from burning substances or agents held by hand. Interstitial Lung Diseases cessation is also important, as well as avoiding stress.

Walking Exercise Strategy

Exercising, such as walking regularly at least 30 continuous minutes 3 times per week, can improve symptoms by encouraging the formation of new collateral blood vessels and improving muscle efficiency. Many patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship experience a dramatic increase in the distance they can walk without pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship also benefit from a vascular rehabilitation program involving 45 minutes of supervised exercise weekly.[21]

Pharmacological Treatment

Pharmacological treatment aims to control the modifiable risk factors of atherosclerosis Atherosclerosis Atherosclerosis is a common form of arterial disease in which lipid deposition forms a plaque in the blood vessel walls. Atherosclerosis is an incurable disease, for which there are clearly defined risk factors that often can be reduced through a change in lifestyle and behavior of the patient. Atherosclerosis. Antihypertensives Antihypertensives The 1st-line medication classes for hypertension include thiazide-like diuretics, angiotensin-converting enzyme inhibitors (ACEis), angiotensin II receptor blockers (ARBs), and calcium channel blockers (CCBS). Contraindications, adverse effects, and drug-to-drug interactions are agent specific. Hypertension Drugs, lipid-lowering agents, and anticoagulant medications treat atherosclerosis Atherosclerosis Atherosclerosis is a common form of arterial disease in which lipid deposition forms a plaque in the blood vessel walls. Atherosclerosis is an incurable disease, for which there are clearly defined risk factors that often can be reduced through a change in lifestyle and behavior of the patient. Atherosclerosis and its complications.

In addition to improving hemoglobin A1c Hemoglobin A1c Products of non-enzymatic reactions between glucose and hemoglobin a, occurring as a minor fraction of the hemoglobin components of human erythrocytes. Hemoglobin a1c is hemoglobin a with glucose covalently bound to the terminal valine of the beta chain. Glycated hemoglobin a is used as an index of the average blood sugar level over a lifetime of erythrocytes. Diabetes Mellitus ( HbA1c HbA1c Products of non-enzymatic reactions between glucose and hemoglobin a, occurring as a minor fraction of the hemoglobin components of human erythrocytes. Hemoglobin a1c is hemoglobin a with glucose covalently bound to the terminal valine of the beta chain. Glycated hemoglobin a is used as an index of the average blood sugar level over a lifetime of erythrocytes. Diabetes Mellitus) levels in adults with type 2 diabetes Diabetes Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus, glucagon-like peptide 1 Glucagon-like peptide 1 A peptide of 36 or 37 amino acids that is derived from proglucagon and mainly produced by the intestinal l cells. Glp-1(1-37 or 1-36) is further n-terminally truncated resulting in glp-1(7-37) or glp-1-(7-36) which can be amidated. These glp-1 peptides are known to enhance glucose-dependent insulin release, suppress glucagon release and gastric emptying, lower blood glucose, and reduce food intake. Insulinomas receptor Receptor Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors agonists (GLP-1RAs), such as liraglutide and semaglutide, have been approved to reduce the risk of major adverse cardiovascular events (MACE) in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with established cardiovascular disease (CVD) or multiple cardiovascular risk factors. Similarly, sodium-glucose cotransporter 2 inhibitors (SGLT2is), including empagliflozin Empagliflozin Non-insulinotropic Diabetes Drugs and canagliflozin Canagliflozin Non-insulinotropic Diabetes Drugs, have been shown to decrease the risk of primary composite cardiovascular outcomes in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with type 2 diabetes Diabetes Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus who are at high risk for cardiovascular events.[35]

Complications

Complications include ischemic heart disease Ischemic heart disease Coronary heart disease (CHD), or ischemic heart disease, describes a situation in which an inadequate supply of blood to the myocardium exists due to a stenosis of the coronary arteries, typically from atherosclerosis. Coronary Heart Disease ( IHD IHD Coronary heart disease (CHD), or ischemic heart disease, describes a situation in which an inadequate supply of blood to the myocardium exists due to a stenosis of the coronary arteries, typically from atherosclerosis. Coronary Heart Disease), angina pectoris Angina pectoris The symptom of paroxysmal pain consequent to myocardial ischemia usually of distinctive character, location and radiation. It is thought to be provoked by a transient stressful situation during which the oxygen requirements of the myocardium exceed that supplied by the coronary circulation. Stable and Unstable Angina, cerebrovascular disease, stroke, peripheral artery disease Peripheral artery disease Peripheral artery disease (PAD) is obstruction of the arterial lumen resulting in decreased blood flow to the distal limbs. The disease can be a result of atherosclerosis or thrombosis. Patients may be asymptomatic or have progressive claudication, skin discoloration, ischemic ulcers, or gangrene. Peripheral Artery Disease (PAD), and renal artery Renal artery A branch of the abdominal aorta which supplies the kidneys, adrenal glands and ureters. Glomerular Filtration stenosis Stenosis Hypoplastic Left Heart Syndrome (HLHS). Subclavian steal Subclavian steal A clinically significant reduction in blood supply to the brain stem and cerebellum (i.e., vertebrobasilar insufficiency) resulting from reversal of blood flow through the vertebral artery from occlusion or stenosis of the proximal subclavian or brachiocephalic artery. Common symptoms include vertigo, syncope, and intermittent claudication of the involved upper extremity. Subclavian steal may also occur in asymptomatic individuals. Subclavian Steal Syndrome syndrome and mesenteric stenosis Stenosis Hypoplastic Left Heart Syndrome (HLHS) can also result from chronic arterial stenosis Stenosis Hypoplastic Left Heart Syndrome (HLHS).

Acute vascular occlusions can also cause complications. Mesenteric infarction, renal or splenic infarction Splenic Infarction Insufficiency of arterial or venous blood supply to the spleen due to emboli, thrombi, vascular torsion, or pressure that produces a macroscopic area of necrosis. . Imaging of the Spleen, transient ischemic attack Transient ischemic attack Transient ischemic attack (TIA) is a temporary episode of neurologic dysfunction caused by ischemia without infarction that resolves completely when blood supply is restored. Transient ischemic attack is a neurologic emergency that warrants urgent medical attention. Transient Ischemic Attack (TIA) ( TIA TIA Transient ischemic attack (TIA) is a temporary episode of neurologic dysfunction caused by ischemia without infarction that resolves completely when blood supply is restored. Transient ischemic attack is a neurologic emergency that warrants urgent medical attention. Transient Ischemic Attack (TIA)), and stroke are seen due to thrombi or emboli occluding an already atherosclerotic artery. Aneurysms at various vessel segments, such as infrarenal or thoracic aortic aneurysms (and possible thoracic aortic dissection Aortic dissection Aortic dissection occurs due to shearing stress from pulsatile pressure causing a tear in the tunica intima of the aortic wall. This tear allows blood to flow into the media, creating a "false lumen." Aortic dissection is most commonly caused by uncontrolled hypertension. Aortic Dissection), as well as iliac or popliteal aneurysms, are potential consequences of atherosclerosis Atherosclerosis Atherosclerosis is a common form of arterial disease in which lipid deposition forms a plaque in the blood vessel walls. Atherosclerosis is an incurable disease, for which there are clearly defined risk factors that often can be reduced through a change in lifestyle and behavior of the patient. Atherosclerosis.

Prevention

Modifiable risk factor reduction is essential. Prevention aims primarily to promote a healthy diet, get adequate physical activity with aerobic exercise, and control underlying diseases like diabetes Diabetes Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus mellitus and hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension. Smoking Smoking Willful or deliberate act of inhaling and exhaling smoke from burning substances or agents held by hand. Interstitial Lung Diseases cessation is the most important measure in preventing atherosclerosis Atherosclerosis Atherosclerosis is a common form of arterial disease in which lipid deposition forms a plaque in the blood vessel walls. Atherosclerosis is an incurable disease, for which there are clearly defined risk factors that often can be reduced through a change in lifestyle and behavior of the patient. Atherosclerosis and its complications.

Dyslipidemia

Definition

Dyslipidemia is a disorder of lipid metabolism Lipid Metabolism Lipid metabolism is the processing of lipids for energy use, energy storage, and structural component production. Lipid metabolism uses fats from dietary sources or from fat stores in the body. A complex series of processes involving digestion, absorption, and transport are required for the proper metabolism of lipids. Lipid Metabolism that is clinically defined as the presence of one of the following abnormalities: elevated plasma Plasma The residual portion of blood that is left after removal of blood cells by centrifugation without prior blood coagulation. Transfusion Products triglycerides Triglycerides Fatty Acids and Lipids ( TG Tg Thyroid Hormones), elevated total cholesterol Cholesterol The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. Cholesterol Metabolism (TC), high levels of low-density lipoprotein Low-density lipoprotein A class of lipoproteins of small size (18-25 nm) and light (1. 019-1. 063 g/ml) particles with a core composed mainly of cholesterol esters and smaller amounts of triglycerides. The surface monolayer consists mostly of phospholipids, a single copy of apolipoprotein B-100, and free cholesterol molecules. The main ldl function is to transport cholesterol and cholesterol esters to extrahepatic tissues. Cholesterol Metabolism (LDL), and decreased high-density lipoprotein High-density lipoprotein A class of lipoproteins of small size (4-13 nm) and dense (greater than 1. 063 g/ml) particles. HDL lipoproteins, synthesized in the liver without a lipid core, accumulate cholesterol esters from peripheral tissues and transport them to the liver for re-utilization or elimination from the body (the reverse cholesterol transport). Their major protein component is apolipoprotein A-I. HDL also shuttle apolipoproteins C and apolipoproteins E to and from triglyceride-rich lipoproteins during their catabolism. Hdl plasma level has been inversely correlated with the risk of cardiovascular diseases. Cholesterol Metabolism (HDL). The specific population values will differ according to age, gender Gender Gender Dysphoria, and race. It is one of the leading causes of the development of atherosclerosis Atherosclerosis Atherosclerosis is a common form of arterial disease in which lipid deposition forms a plaque in the blood vessel walls. Atherosclerosis is an incurable disease, for which there are clearly defined risk factors that often can be reduced through a change in lifestyle and behavior of the patient. Atherosclerosis.

Etiology

Causes of dyslipidemia can be primary as in familial hypercholesterolemia Familial hypercholesterolemia Lipid Disorders or secondary to underlying diseases such as diabetes Diabetes Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus mellitus, hypothyroidism Hypothyroidism Hypothyroidism is a condition characterized by a deficiency of thyroid hormones. Iodine deficiency is the most common cause worldwide, but Hashimoto's disease (autoimmune thyroiditis) is the leading cause in non-iodine-deficient regions. Hypothyroidism, nephrotic syndrome Nephrotic syndrome Nephrotic syndrome is characterized by severe proteinuria, hypoalbuminemia, and peripheral edema. In contrast, the nephritic syndromes present with hematuria, variable loss of renal function, and hypertension, although there is sometimes overlap of > 1 glomerular disease in the same individual. Nephrotic Syndrome, and hepatic disorders.

Clinical Features

Dyslipidemia is usually asymptomatic and is seen in >70% of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with premature Premature Childbirth before 37 weeks of pregnancy (259 days from the first day of the mother's last menstrual period, or 245 days after fertilization). Necrotizing Enterocolitis coronary heart disease Coronary heart disease Coronary heart disease (CHD), or ischemic heart disease, describes a situation in which an inadequate supply of blood to the myocardium exists due to a stenosis of the coronary arteries, typically from atherosclerosis. Coronary Heart Disease. Yellowish plaques with lipid-laden histiocytes Histiocytes Macrophages found in the tissues, as opposed to those found in the blood (monocytes) or serous cavities (serous membrane). Chronic Granulomatous Disease surrounding blood vessels are sometimes found on the skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions around patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship’ eyes ( xanthelasmas Xanthelasmas Lipid Disorders) or over the joints or tendons ( xanthomas Xanthomas Lipid Disorders). Other clinical features of dyslipidemia include corneal arcus Corneal arcus A corneal disease in which there is a deposition of phospholipid and cholesterol in the corneal stroma and anterior sclera. Cardiovascular Examination (“ arcus senilis Arcus senilis A corneal disease in which there is a deposition of phospholipid and cholesterol in the corneal stroma and anterior sclera. Lipid Disorders”) and hepatosplenomegaly Hepatosplenomegaly Cytomegalovirus. Dyslipidemia is often diagnosed on routine investigations or after a cardiovascular event such as a myocardial infarction Myocardial infarction MI is ischemia and death of an area of myocardial tissue due to insufficient blood flow and oxygenation, usually from thrombus formation on a ruptured atherosclerotic plaque in the epicardial arteries. Clinical presentation is most commonly with chest pain, but women and patients with diabetes may have atypical symptoms. Myocardial Infarction or stroke.

An important cause of dyslipidemia is familial hypercholesterolemia Familial hypercholesterolemia Lipid Disorders (FH), one of the most common serious hereditary disorders, with heterozygotes occurring in 1/250 people. It should be suspected in individuals with fasting LDL cholesterol Cholesterol The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. Cholesterol Metabolism levels above 190 mg/dL or non-HDL cholesterol Cholesterol The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. Cholesterol Metabolism above 220 mg/dL or in family members of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with total cholesterol Cholesterol The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. Cholesterol Metabolism above 240 mg/dL. FH has an autosomal dominant Autosomal dominant Autosomal inheritance, both dominant and recessive, refers to the transmission of genes from the 22 autosomal chromosomes. Autosomal dominant diseases are expressed when only 1 copy of the dominant allele is inherited. Autosomal Recessive and Autosomal Dominant Inheritance pattern of inheritance and is caused by mutations in the genes Genes A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. DNA Types and Structure encoding the LDL receptor Receptor Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors (85% cases), ApoB protein (5%–10% cases), or activating mutations of PCSK9 (1%–2% cases). Hypercholesterolemia Hypercholesterolemia A condition with abnormally high levels of cholesterol in the blood. It is defined as a cholesterol value exceeding the 95th percentile for the population. Lipid Disorders develops as a consequence of impaired transport of LDL into the cells. Homozygotes have a greater increase in serum cholesterol Cholesterol The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. Cholesterol Metabolism and a higher frequency of ischemic heart disease Ischemic heart disease Coronary heart disease (CHD), or ischemic heart disease, describes a situation in which an inadequate supply of blood to the myocardium exists due to a stenosis of the coronary arteries, typically from atherosclerosis. Coronary Heart Disease.[22]

Frederickson Classification of Lipid Disorders Lipid disorders An abnormal amount of lipid in blood is called dyslipidemia, which includes abnormal levels of cholesterol, triglycerides, and/or lipoproteins. Dyslipidemia may be primary (familial) or secondary (acquired). Both primary and secondary causes can lead to the development of premature cardiovascular (atherosclerosis) disease. Lipid Disorders  [23]

Type	Typical Lipid Levels	Lipoprotein Abnormality
I	TG Tg Thyroid Hormones > 99th percentile	Chylomicrons
IIa	TC > 90th percentile; apoB ≥ 90th percentile (depends on type)	LDL
IIb	Depending on type, TC and/or TG Tg Thyroid Hormones ≥ 90th percentile and apo B ≥ 90th percentile	LDL and VLDL
III	TC and TG Tg Thyroid Hormones > 90th percentile	Remnants of VLDL (Intermediate density lipoprotein) and chylomicrons
IV	TC > 90th percentile; depending on type, +/- TG Tg Thyroid Hormones > 90th percentile, or low HDL	VLDL
V	TG Tg Thyroid Hormones > 99th percentile	VLDL and chylomicrons

Treatment

Non-Pharmacological Treatment (Lifestyle Modification)

Lifestyle modifications remain an essential therapeutic option for controlling dyslipidemia. These modifications include:

• Dietary changes: reduce saturated fat intake
• Weight reduction if overweight
• Daily aerobic exercise or regular Regular Insulin exercise

High-yield fact: Regular Regular Insulin exercise is proven to increase HDL and decrease LDL levels.[24]

Pharmacological Treatment

Statin therapy

The American Heart Association American Heart Association A voluntary organization concerned with the prevention and treatment of heart and vascular diseases. Heart Failure recommends a moderate-intensity statin for primary prevention of ASCVD in adults ages 40–75 without diabetes Diabetes Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus mellitus who have a 10-year atherosclerotic cardiovascular disease risk of 7.5–20%.[25]

High-intensity statin therapy is recommended for high-risk patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with a10-year ASCVD risk > 20%) or those who already have ASCVD.

Note 1:

• The goal is to achieve a 50% reduction of the baseline LDL value. 

Note 2:

• High-intensity statins Statins Statins are competitive inhibitors of HMG-CoA reductase in the liver. HMG-CoA reductase is the rate-limiting step in cholesterol synthesis. Inhibition results in lowered intrahepatocytic cholesterol formation, resulting in up-regulation of LDL receptors and, ultimately, lowering levels of serum LDL and triglycerides. Statins include rosuvastatin Rosuvastatin A hydroxymethylglutaryl-coa-reductase inhibitor, or statin, that reduces the plasma concentrations of ldl-cholesterol; apolipoprotein b, and triglycerides while increasing hdl-cholesterol levels in patients with hypercholesterolemia and those at risk for cardiovascular diseases. Statins 20 or 40 mg and atorvastatin Atorvastatin A pyrrole and heptanoic acid derivative, hydroxymethylglutaryl-CoA reductase inhibitor (statin), and anticholesteremic agent that is used to reduce serum levels of ldl-cholesterol; apolipoprotein b; and triglycerides. It is used to increase serum levels of hdl-cholesterol in the treatment of hyperlipidemias, and for the prevention of cardiovascular diseases in patients with multiple risk factors. Statins 40 or 80 mg.
• Moderate-intensity statins Statins Statins are competitive inhibitors of HMG-CoA reductase in the liver. HMG-CoA reductase is the rate-limiting step in cholesterol synthesis. Inhibition results in lowered intrahepatocytic cholesterol formation, resulting in up-regulation of LDL receptors and, ultimately, lowering levels of serum LDL and triglycerides. Statins include rosuvastatin Rosuvastatin A hydroxymethylglutaryl-coa-reductase inhibitor, or statin, that reduces the plasma concentrations of ldl-cholesterol; apolipoprotein b, and triglycerides while increasing hdl-cholesterol levels in patients with hypercholesterolemia and those at risk for cardiovascular diseases. Statins 5 or 10 mg and atorvastatin Atorvastatin A pyrrole and heptanoic acid derivative, hydroxymethylglutaryl-CoA reductase inhibitor (statin), and anticholesteremic agent that is used to reduce serum levels of ldl-cholesterol; apolipoprotein b; and triglycerides. It is used to increase serum levels of hdl-cholesterol in the treatment of hyperlipidemias, and for the prevention of cardiovascular diseases in patients with multiple risk factors. Statins 10 or 20 mg.

Note 3: Mechanism of action of statins Statins Statins are competitive inhibitors of HMG-CoA reductase in the liver. HMG-CoA reductase is the rate-limiting step in cholesterol synthesis. Inhibition results in lowered intrahepatocytic cholesterol formation, resulting in up-regulation of LDL receptors and, ultimately, lowering levels of serum LDL and triglycerides. Statins, or HMG-CoA reductase HMG-CoA reductase Enzymes that catalyze the reversible reduction of alpha-carboxyl group of 3-hydroxy-3-methylglutaryl-coenzyme A to yield mevalonic acid. Cholesterol Metabolism inhibitors: 

• The primary mechanism is by inhibition of the enzyme  3-hydroxy-3-methylglutaryl-coenzyme A reductase. This enzyme is crucial in the mevalonate Mevalonate Cholesterol Metabolism pathway, which is responsible for cholesterol Cholesterol The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. Cholesterol Metabolism biosynthesis Biosynthesis The biosynthesis of peptides and proteins on ribosomes, directed by messenger RNA, via transfer RNA that is charged with standard proteinogenic amino acids. Virology. By inhibiting this pathway, statins Statins Statins are competitive inhibitors of HMG-CoA reductase in the liver. HMG-CoA reductase is the rate-limiting step in cholesterol synthesis. Inhibition results in lowered intrahepatocytic cholesterol formation, resulting in up-regulation of LDL receptors and, ultimately, lowering levels of serum LDL and triglycerides. Statins effectively reduce the synthesis Synthesis Polymerase Chain Reaction (PCR) of cholesterol Cholesterol The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. Cholesterol Metabolism, particularly low-density lipoprotein Low-density lipoprotein A class of lipoproteins of small size (18-25 nm) and light (1. 019-1. 063 g/ml) particles with a core composed mainly of cholesterol esters and smaller amounts of triglycerides. The surface monolayer consists mostly of phospholipids, a single copy of apolipoprotein B-100, and free cholesterol molecules. The main ldl function is to transport cholesterol and cholesterol esters to extrahepatic tissues. Cholesterol Metabolism cholesterol Cholesterol The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. Cholesterol Metabolism (LDL-C), which is a major contributor to atherosclerosis Atherosclerosis Atherosclerosis is a common form of arterial disease in which lipid deposition forms a plaque in the blood vessel walls. Atherosclerosis is an incurable disease, for which there are clearly defined risk factors that often can be reduced through a change in lifestyle and behavior of the patient. Atherosclerosis and cardiovascular disease.
• Beyond their lipid-lowering effects, statins Statins Statins are competitive inhibitors of HMG-CoA reductase in the liver. HMG-CoA reductase is the rate-limiting step in cholesterol synthesis. Inhibition results in lowered intrahepatocytic cholesterol formation, resulting in up-regulation of LDL receptors and, ultimately, lowering levels of serum LDL and triglycerides. Statins exhibit significant anti-inflammatory properties. These effects are mediated through several mechanisms:
  • Statins Statins Statins are competitive inhibitors of HMG-CoA reductase in the liver. HMG-CoA reductase is the rate-limiting step in cholesterol synthesis. Inhibition results in lowered intrahepatocytic cholesterol formation, resulting in up-regulation of LDL receptors and, ultimately, lowering levels of serum LDL and triglycerides. Statins enhance endothelial function by increasing nitric oxide Nitric Oxide A free radical gas produced endogenously by a variety of mammalian cells, synthesized from arginine by nitric oxide synthase. Nitric oxide is one of the endothelium-dependent relaxing factors released by the vascular endothelium and mediates vasodilation. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic guanylate cyclase and thus elevates intracellular levels of cyclic gmp. Pulmonary Hypertension Drugs bioavailability Bioavailability Pharmacokinetics and Pharmacodynamics, which has vasodilatory and anti-inflammatory effects.
  • They also reduce the expression of pro-inflammatory cytokines Cytokines Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner. Adaptive Immune Response and adhesion Adhesion The process whereby platelets adhere to something other than platelets, e.g., collagen; basement membrane; microfibrils; or other 'foreign' surfaces. Coagulation Studies molecules, thereby decreasing leukocyte adhesion Leukocyte adhesion Leukocyte Adhesion Deficiency Type 1 and transmigration Transmigration Leukocyte Adhesion Deficiency Type 1 across the endothelium Endothelium A layer of epithelium that lines the heart, blood vessels (vascular endothelium), lymph vessels (lymphatic endothelium), and the serous cavities of the body. Arteries: Histology.
  • Statins Statins Statins are competitive inhibitors of HMG-CoA reductase in the liver. HMG-CoA reductase is the rate-limiting step in cholesterol synthesis. Inhibition results in lowered intrahepatocytic cholesterol formation, resulting in up-regulation of LDL receptors and, ultimately, lowering levels of serum LDL and triglycerides. Statins modulate the immune response by affecting both innate and adaptive immunity. They inhibit the activation of T-cells and monocytes Monocytes Large, phagocytic mononuclear leukocytes produced in the vertebrate bone marrow and released into the blood; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles. Innate Immunity: Phagocytes and Antigen Presentation, reduce the production of reactive oxygen species Reactive oxygen species Molecules or ions formed by the incomplete one-electron reduction of oxygen. These reactive oxygen intermediates include singlet oxygen; superoxides; peroxides; hydroxyl radical; and hypochlorous acid. They contribute to the microbicidal activity of phagocytes, regulation of signal transduction and gene expression, and the oxidative damage to nucleic acids; proteins; and lipids. Nonalcoholic Fatty Liver Disease, and decrease the expression of major histocompatibility complex Major histocompatibility complex The genetic region which contains the loci of genes which determine the structure of the serologically defined (sd) and lymphocyte-defined (ld) transplantation antigens, genes which control the structure of the immune response-associated antigens, human; the immune response genes which control the ability of an animal to respond immunologically to antigenic stimuli, and genes which determine the structure and/or level of the first four components of complement. Innate Immunity: Phagocytes and Antigen Presentation (MHC) class II molecules on endothelial cells. These actions collectively contribute to the stabilization of atherosclerotic plaques and reduction of vascular inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body's defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation.
  • The anti-inflammatory properties of statins Statins Statins are competitive inhibitors of HMG-CoA reductase in the liver. HMG-CoA reductase is the rate-limiting step in cholesterol synthesis. Inhibition results in lowered intrahepatocytic cholesterol formation, resulting in up-regulation of LDL receptors and, ultimately, lowering levels of serum LDL and triglycerides. Statins are thought to contribute to their ability to prolong life by reducing the risk of cardiovascular events. This is supported by evidence showing that statins Statins Statins are competitive inhibitors of HMG-CoA reductase in the liver. HMG-CoA reductase is the rate-limiting step in cholesterol synthesis. Inhibition results in lowered intrahepatocytic cholesterol formation, resulting in up-regulation of LDL receptors and, ultimately, lowering levels of serum LDL and triglycerides. Statins lower levels of C-reactive protein (CRP), an independent marker of cardiovascular risk, even in individuals with low LDL-C levels. The reduction in vascular inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body's defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation and improvement in endothelial function are key factors in the primary and secondary prevention of cardiovascular events, thereby enhancing overall survival.[36,37,38]

Contraindications Contraindications A condition or factor associated with a recipient that makes the use of a drug, procedure, or physical agent improper or inadvisable. Contraindications may be absolute (life threatening) or relative (higher risk of complications in which benefits may outweigh risks). Noninvasive Ventilation to Statins Statins Statins are competitive inhibitors of HMG-CoA reductase in the liver. HMG-CoA reductase is the rate-limiting step in cholesterol synthesis. Inhibition results in lowered intrahepatocytic cholesterol formation, resulting in up-regulation of LDL receptors and, ultimately, lowering levels of serum LDL and triglycerides. Statins

Statins Statins Statins are competitive inhibitors of HMG-CoA reductase in the liver. HMG-CoA reductase is the rate-limiting step in cholesterol synthesis. Inhibition results in lowered intrahepatocytic cholesterol formation, resulting in up-regulation of LDL receptors and, ultimately, lowering levels of serum LDL and triglycerides. Statins are contraindicated in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with active liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy disease and pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care. Although the incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency of recorded adverse effects is low, the side effect of musculoskeletal pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways is seen clinically in 22% of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship on statins Statins Statins are competitive inhibitors of HMG-CoA reductase in the liver. HMG-CoA reductase is the rate-limiting step in cholesterol synthesis. Inhibition results in lowered intrahepatocytic cholesterol formation, resulting in up-regulation of LDL receptors and, ultimately, lowering levels of serum LDL and triglycerides. Statins (compared to 17% of those not on statins Statins Statins are competitive inhibitors of HMG-CoA reductase in the liver. HMG-CoA reductase is the rate-limiting step in cholesterol synthesis. Inhibition results in lowered intrahepatocytic cholesterol formation, resulting in up-regulation of LDL receptors and, ultimately, lowering levels of serum LDL and triglycerides. Statins). The main side effects of statins Statins Statins are competitive inhibitors of HMG-CoA reductase in the liver. HMG-CoA reductase is the rate-limiting step in cholesterol synthesis. Inhibition results in lowered intrahepatocytic cholesterol formation, resulting in up-regulation of LDL receptors and, ultimately, lowering levels of serum LDL and triglycerides. Statins are:

• Myopathies (1%)
• Rhabdomyolysis Rhabdomyolysis Rhabdomyolysis is characterized by muscle necrosis and the release of toxic intracellular contents, especially myoglobin, into the circulation. Rhabdomyolysis (0.2%) 
• Elevated liver function tests Liver function tests Liver function tests, also known as hepatic function panels, are one of the most commonly performed screening blood tests. Such tests are also used to detect, evaluate, and monitor acute and chronic liver diseases. Liver Function Tests (2%) 

Rare side effects of statins Statins Statins are competitive inhibitors of HMG-CoA reductase in the liver. HMG-CoA reductase is the rate-limiting step in cholesterol synthesis. Inhibition results in lowered intrahepatocytic cholesterol formation, resulting in up-regulation of LDL receptors and, ultimately, lowering levels of serum LDL and triglycerides. Statins include confusion, forgetfulness, dementia Dementia Major neurocognitive disorders (NCD), also known as dementia, are a group of diseases characterized by decline in a person's memory and executive function. These disorders are progressive and persistent diseases that are the leading cause of disability among elderly people worldwide. Major Neurocognitive Disorders, depression, and erectile dysfunction Erectile Dysfunction Erectile dysfunction (ED) is defined as the inability to achieve or maintain a penile erection, resulting in difficulty to perform penetrative sexual intercourse. Local penile factors and systemic diseases, including diabetes, cardiac disease, and neurological disorders, can cause ED. Erectile Dysfunction. 

In adults with coronary artery Coronary Artery Truncus Arteriosus disease, both rosuvastatin Rosuvastatin A hydroxymethylglutaryl-coa-reductase inhibitor, or statin, that reduces the plasma concentrations of ldl-cholesterol; apolipoprotein b, and triglycerides while increasing hdl-cholesterol levels in patients with hypercholesterolemia and those at risk for cardiovascular diseases. Statins and atorvastatin Atorvastatin A pyrrole and heptanoic acid derivative, hydroxymethylglutaryl-CoA reductase inhibitor (statin), and anticholesteremic agent that is used to reduce serum levels of ldl-cholesterol; apolipoprotein b; and triglycerides. It is used to increase serum levels of hdl-cholesterol in the treatment of hyperlipidemias, and for the prevention of cardiovascular diseases in patients with multiple risk factors. Statins were equally effective in reducing the composite outcome of all-cause death, myocardial infarction Myocardial infarction MI is ischemia and death of an area of myocardial tissue due to insufficient blood flow and oxygenation, usually from thrombus formation on a ruptured atherosclerotic plaque in the epicardial arteries. Clinical presentation is most commonly with chest pain, but women and patients with diabetes may have atypical symptoms. Myocardial Infarction, stroke, or any coronary revascularization Revascularization Thromboangiitis Obliterans (Buerger’s Disease) over three years. Rosuvastatin Rosuvastatin A hydroxymethylglutaryl-coa-reductase inhibitor, or statin, that reduces the plasma concentrations of ldl-cholesterol; apolipoprotein b, and triglycerides while increasing hdl-cholesterol levels in patients with hypercholesterolemia and those at risk for cardiovascular diseases. Statins was linked to lower LDL cholesterol Cholesterol The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. Cholesterol Metabolism levels but also to a higher incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency of new-onset diabetes Diabetes Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus requiring antidiabetic medications and a greater likelihood of cataract Cataract Partial or complete opacity on or in the lens or capsule of one or both eyes, impairing vision or causing blindness. The many kinds of cataract are classified by their morphology (size, shape, location) or etiology (cause and time of occurrence). Neurofibromatosis Type 2 surgery compared to atorvastatin Atorvastatin A pyrrole and heptanoic acid derivative, hydroxymethylglutaryl-CoA reductase inhibitor (statin), and anticholesteremic agent that is used to reduce serum levels of ldl-cholesterol; apolipoprotein b; and triglycerides. It is used to increase serum levels of hdl-cholesterol in the treatment of hyperlipidemias, and for the prevention of cardiovascular diseases in patients with multiple risk factors. Statins.[32]

The introduction of statins Statins Statins are competitive inhibitors of HMG-CoA reductase in the liver. HMG-CoA reductase is the rate-limiting step in cholesterol synthesis. Inhibition results in lowered intrahepatocytic cholesterol formation, resulting in up-regulation of LDL receptors and, ultimately, lowering levels of serum LDL and triglycerides. Statins to manage hyperlipidemia has improved the prognosis Prognosis A prediction of the probable outcome of a disease based on a individual's condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas of IHD IHD Coronary heart disease (CHD), or ischemic heart disease, describes a situation in which an inadequate supply of blood to the myocardium exists due to a stenosis of the coronary arteries, typically from atherosclerosis. Coronary Heart Disease.

Statins Statins Statins are competitive inhibitors of HMG-CoA reductase in the liver. HMG-CoA reductase is the rate-limiting step in cholesterol synthesis. Inhibition results in lowered intrahepatocytic cholesterol formation, resulting in up-regulation of LDL receptors and, ultimately, lowering levels of serum LDL and triglycerides. Statins are also effective in lowering the risk of recurrent stroke in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with a previous history of cerebrovascular disease. However, a definite mortality Mortality All deaths reported in a given population. Measures of Health Status benefit has been more challenging to demonstrate consistently with statin treatment. Intense LDL-C lowering lowers the risk of all-cause death in those at very high risk [26]. Initiating statins Statins Statins are competitive inhibitors of HMG-CoA reductase in the liver. HMG-CoA reductase is the rate-limiting step in cholesterol synthesis. Inhibition results in lowered intrahepatocytic cholesterol formation, resulting in up-regulation of LDL receptors and, ultimately, lowering levels of serum LDL and triglycerides. Statins to lower LDL cholesterol Cholesterol The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. Cholesterol Metabolism levels in the acute setting of a cerebrovascular accident Cerebrovascular accident An ischemic stroke (also known as cerebrovascular accident) is an acute neurologic injury that occurs as a result of brain ischemia; this condition may be due to cerebral blood vessel occlusion by thrombosis or embolism, or rarely due to systemic hypoperfusion. Ischemic Stroke was proven to improve clinical outcomes and reduce the disability Disability Determination of the degree of a physical, mental, or emotional handicap. The diagnosis is applied to legal qualification for benefits and income under disability insurance and to eligibility for social security and workman's compensation benefits. ABCDE Assessment of such patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship.

Non-statin therapy

PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitors are now being used to decrease LDL cholesterol Cholesterol The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. Cholesterol Metabolism levels associated with cardiovascular disease. PSCK9 is an enzyme produced in the liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy that binds to the LDL receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors on hepatocytes Hepatocytes The main structural component of the liver. They are specialized epithelial cells that are organized into interconnected plates called lobules. Liver: Anatomy, resulting in higher plasma Plasma The residual portion of blood that is left after removal of blood cells by centrifugation without prior blood coagulation. Transfusion Products LDL cholesterol Cholesterol The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. Cholesterol Metabolism levels. Blocking this enzyme with monoclonal antibodies Monoclonal antibodies Antibodies produced by a single clone of cells. Ebolavirus and Marburgvirus (e.g., alirocumab Alirocumab Lipid Control Drugs, evolocumab Evolocumab Lipid Control Drugs) is associated with lower rates of myocardial infarction Myocardial infarction MI is ischemia and death of an area of myocardial tissue due to insufficient blood flow and oxygenation, usually from thrombus formation on a ruptured atherosclerotic plaque in the epicardial arteries. Clinical presentation is most commonly with chest pain, but women and patients with diabetes may have atypical symptoms. Myocardial Infarction and stroke.[29, 30]

Ezetimibe Ezetimibe An azetidine derivative and anticholesteremic agent that inhibits intestinal sterol absorption. It is used to reduce total cholesterol; ldl cholesterol, and apolipoproteins B in the treatment of hyperlipidemias. Lipid Control Drugs inhibits cholesterol Cholesterol The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. Cholesterol Metabolism absorption Absorption Absorption involves the uptake of nutrient molecules and their transfer from the lumen of the GI tract across the enterocytes and into the interstitial space, where they can be taken up in the venous or lymphatic circulation. Digestion and Absorption at the brush border Brush border Tubular System of the small intestine Small intestine The small intestine is the longest part of the GI tract, extending from the pyloric orifice of the stomach to the ileocecal junction. The small intestine is the major organ responsible for chemical digestion and absorption of nutrients. It is divided into 3 segments: the duodenum, the jejunum, and the ileum. Small Intestine: Anatomy via the sterol Sterol Steroids with a hydroxyl group at c-3 and most of the skeleton of cholestane. Additional carbon atoms may be present in the side chain. Mycoplasma transporter, Niemann-Pick C1-Like1 (NPC1L1), and is offered to patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship who cannot tolerate statins Statins Statins are competitive inhibitors of HMG-CoA reductase in the liver. HMG-CoA reductase is the rate-limiting step in cholesterol synthesis. Inhibition results in lowered intrahepatocytic cholesterol formation, resulting in up-regulation of LDL receptors and, ultimately, lowering levels of serum LDL and triglycerides. Statins. PCSK9 monoclonal antibodies Monoclonal antibodies Antibodies produced by a single clone of cells. Ebolavirus and Marburgvirus ( alirocumab Alirocumab Lipid Control Drugs and evolocumab Evolocumab Lipid Control Drugs) bind BIND Hyperbilirubinemia of the Newborn free plasma Plasma The residual portion of blood that is left after removal of blood cells by centrifugation without prior blood coagulation. Transfusion Products PCSK9, an enzyme that degrades the receptor Receptor Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors for LDL (LDL (LDL-R), leading to higher hepatic LDL-R expression and lower plasma Plasma The residual portion of blood that is left after removal of blood cells by centrifugation without prior blood coagulation. Transfusion Products LDL-C levels. This treatment is recommended for those whose LDL-C remains above 70 mg/dL. [27,28]. Other lipid-lowering medications that can be used to lower the LDL cholesterol Cholesterol The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. Cholesterol Metabolism level include icosapent ethyl (an omega-3 fatty acid) and fibrates Fibrates Lipid Control Drugs (more often used for hypertriglyceridemia Hypertriglyceridemia A condition of elevated levels of triglycerides in the blood. Lipid Disorders). Bile acid sequestrants Bile Acid Sequestrants Antidiarrheal Drugs (e.g., cholestyramine Cholestyramine A strongly basic anion exchange resin whose main constituent is polystyrene trimethylbenzylammonium cl(-) anion. Lipid Control Drugs, colestipol Colestipol Highly crosslinked and insoluble basic anion exchange resin used as anticholesteremic. It may also may reduce triglyceride levels. Lipid Control Drugs, and colesevelam Colesevelam An allylamine derivative that binds bile acids in the intestine and is used as an anticholesteremic agent in the treatment of hypercholesterolemia and hyperlipidemias. Lipid Control Drugs) and nicotinic acid Nicotinic acid A water-soluble vitamin of the B complex occurring in various animal and plant tissues. It is required by the body for the formation of coenzymes nad and nadp. It has pellagra-curative, vasodilating, and antilipemic properties. Lipid Control Drugs ( niacin Niacin A water-soluble vitamin of the B complex occurring in various animal and plant tissues. It is required by the body for the formation of coenzymes nad and NADP. It has pellagra-curative, vasodilating, and antilipemic properties. Lipid Control Drugs) are rarely used because of their side effects; however, nicotinic acid Nicotinic acid A water-soluble vitamin of the B complex occurring in various animal and plant tissues. It is required by the body for the formation of coenzymes nad and nadp. It has pellagra-curative, vasodilating, and antilipemic properties. Lipid Control Drugs is used to lower lipoprotein(a). 

Bempedoic acid Bempedoic Acid Lipid Control Drugs, an ATP citrate lyase inhibitor, effectively lowers low-density lipoprotein Low-density lipoprotein A class of lipoproteins of small size (18-25 nm) and light (1. 019-1. 063 g/ml) particles with a core composed mainly of cholesterol esters and smaller amounts of triglycerides. The surface monolayer consists mostly of phospholipids, a single copy of apolipoprotein B-100, and free cholesterol molecules. The main ldl function is to transport cholesterol and cholesterol esters to extrahepatic tissues. Cholesterol Metabolism (LDL) cholesterol Cholesterol The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. Cholesterol Metabolism levels and has a low incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency of muscle-related side effects. While its impact on cardiovascular outcomes is still being evaluated, among patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship intolerant to statins Statins Statins are competitive inhibitors of HMG-CoA reductase in the liver. HMG-CoA reductase is the rate-limiting step in cholesterol synthesis. Inhibition results in lowered intrahepatocytic cholesterol formation, resulting in up-regulation of LDL receptors and, ultimately, lowering levels of serum LDL and triglycerides. Statins, bempedoic acid Bempedoic Acid Lipid Control Drugs treatment has been linked to a reduced risk of major adverse cardiovascular events, including death from cardiovascular causes, nonfatal myocardial infarction Myocardial infarction MI is ischemia and death of an area of myocardial tissue due to insufficient blood flow and oxygenation, usually from thrombus formation on a ruptured atherosclerotic plaque in the epicardial arteries. Clinical presentation is most commonly with chest pain, but women and patients with diabetes may have atypical symptoms. Myocardial Infarction, nonfatal stroke, and coronary revascularization Revascularization Thromboangiitis Obliterans (Buerger’s Disease).[33]

In patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with refractory hypercholesterolemia Hypercholesterolemia A condition with abnormally high levels of cholesterol in the blood. It is defined as a cholesterol value exceeding the 95th percentile for the population. Lipid Disorders who maintain high LDL cholesterol Cholesterol The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. Cholesterol Metabolism levels despite maximal lipid-lowering therapy, the risk of atherosclerosis Atherosclerosis Atherosclerosis is a common form of arterial disease in which lipid deposition forms a plaque in the blood vessel walls. Atherosclerosis is an incurable disease, for which there are clearly defined risk factors that often can be reduced through a change in lifestyle and behavior of the patient. Atherosclerosis remains elevated. Evinacumab, a fully human monoclonal antibody targeting angiopoietin-like 3, administered either subcutaneously or intravenously, has been shown to reduce LDL cholesterol Cholesterol The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. Cholesterol Metabolism levels by over 50% at the highest dose.[34]

Review Questions

1. Which vascular area is prone to be affected by atherosclerosis Atherosclerosis Atherosclerosis is a common form of arterial disease in which lipid deposition forms a plaque in the blood vessel walls. Atherosclerosis is an incurable disease, for which there are clearly defined risk factors that often can be reduced through a change in lifestyle and behavior of the patient. Atherosclerosis?
   1. Arteries Arteries Arteries are tubular collections of cells that transport oxygenated blood and nutrients from the heart to the tissues of the body. The blood passes through the arteries in order of decreasing luminal diameter, starting in the largest artery (the aorta) and ending in the small arterioles. Arteries are classified into 3 types: large elastic arteries, medium muscular arteries, and small arteries and arterioles. Arteries: Histology in the extremities
   2. All coronary arteries Arteries Arteries are tubular collections of cells that transport oxygenated blood and nutrients from the heart to the tissues of the body. The blood passes through the arteries in order of decreasing luminal diameter, starting in the largest artery (the aorta) and ending in the small arterioles. Arteries are classified into 3 types: large elastic arteries, medium muscular arteries, and small arteries and arterioles. Arteries: Histology
   3. Intracranial arteries Arteries Arteries are tubular collections of cells that transport oxygenated blood and nutrients from the heart to the tissues of the body. The blood passes through the arteries in order of decreasing luminal diameter, starting in the largest artery (the aorta) and ending in the small arterioles. Arteries are classified into 3 types: large elastic arteries, medium muscular arteries, and small arteries and arterioles. Arteries: Histology
   4. Carotid artery bifurcation
   5. Renal arteries Arteries Arteries are tubular collections of cells that transport oxygenated blood and nutrients from the heart to the tissues of the body. The blood passes through the arteries in order of decreasing luminal diameter, starting in the largest artery (the aorta) and ending in the small arterioles. Arteries are classified into 3 types: large elastic arteries, medium muscular arteries, and small arteries and arterioles. Arteries: Histology
2. What best describes the composition of an atherosclerotic plaque Plaque Primary Skin Lesions?
   1. Cholesterol Cholesterol The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. Cholesterol Metabolism
   2. Lipids Lipids Lipids are a diverse group of hydrophobic organic molecules, which include fats, oils, sterols, and waxes. Fatty Acids and Lipids and cellular debris
   3. Smooth muscle
   4. Fibrin Fibrin A protein derived from fibrinogen in the presence of thrombin, which forms part of the blood clot. Rapidly Progressive Glomerulonephritis
   5. Collagen Collagen A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin; connective tissue; and the organic substance of bones (bone and bones) and teeth (tooth). Connective Tissue: Histology
3. Which of these conditions is not related to atherosclerosis Atherosclerosis Atherosclerosis is a common form of arterial disease in which lipid deposition forms a plaque in the blood vessel walls. Atherosclerosis is an incurable disease, for which there are clearly defined risk factors that often can be reduced through a change in lifestyle and behavior of the patient. Atherosclerosis?
   1. Peripheral artery disease Peripheral artery disease Peripheral artery disease (PAD) is obstruction of the arterial lumen resulting in decreased blood flow to the distal limbs. The disease can be a result of atherosclerosis or thrombosis. Patients may be asymptomatic or have progressive claudication, skin discoloration, ischemic ulcers, or gangrene. Peripheral Artery Disease
   2. Coronary heart disease Coronary heart disease Coronary heart disease (CHD), or ischemic heart disease, describes a situation in which an inadequate supply of blood to the myocardium exists due to a stenosis of the coronary arteries, typically from atherosclerosis. Coronary Heart Disease
   3. Prinzmetal angina Prinzmetal angina Vasospastic angina, also known as prinzmetal or variant angina, is an uncommon cause of chest pain due to transient coronary artery spasms. The pathophysiology is distinguished from stable or unstable angina secondary to atherosclerotic coronary artery disease (CAD). Vasospastic Angina
   4. Stroke
   5. Mesenteric artery stenosis Stenosis Hypoplastic Left Heart Syndrome (HLHS)

Answers: 1-4, 2-2, 3-3