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Lipid Disorders

An abnormal amount of lipid in blood is called dyslipidemia, which includes abnormal levels 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, triglycerides Triglycerides Fatty Acids and Lipids, and/or 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. Dyslipidemia may be primary (familial) or secondary (acquired). Both primary and secondary causes can lead to the development of 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 cardiovascular ( 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) disease. Familial causes are classified according to the Fredrickson system, which looks into the pathology and the lipids Lipids Lipids are a diverse group of hydrophobic organic molecules, which include fats, oils, sterols, and waxes. Fatty Acids and Lipids that are elevated. Certain types do not increase the risk of 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 atherosclerotic disease but still impact overall cardiac risk and chance of cardiovascular events in the future. Screening Screening Preoperative Care, early diagnosis, and strict control and management are the keys to prevention of cardiovascular events.

Last updated: Sep 12, 2022

Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

Overview

Definition

Dyslipidemia: abnormal amounts of lipid in the blood 

  • Hyperlipidemia (HLD): elevated lipids Lipids Lipids are a diverse group of hydrophobic organic molecules, which include fats, oils, sterols, and waxes. Fatty Acids and Lipids in the blood (elevated 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, triglycerides Triglycerides Fatty Acids and Lipids, and/or 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)
  • Hyperlipoproteinemia: elevated levels of LDL, VLDL
  • Hypercholesterolemia: 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 (> 200 mg/dL)
  • Hypertriglyceridemia: elevated triglyceride levels (> 150 mg/dL)

Epidemiology

  • Prevalence Prevalence The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. Measures of Disease Frequency increases with age.
  • 50% of Americans have a high LDL count.
  • Only 35% of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship are adequately treated.
  • 54% of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with HLD have a family history Family History Adult Health Maintenance of atherosclerotic coronary artery disease Coronary artery disease Pathological processes of coronary arteries that may derive from a congenital abnormality, atherosclerotic, or non-atherosclerotic cause. Stable and Unstable Angina (CAD).
  • Men > women
  • Whites > people of color

Pathophysiology

  • Familial causes of dyslipidemia usually result from mutations that result in:
    • Decreased uptake 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 (Lps) by 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 (loss of 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 mediators) 
    • Reduced clearance of triglycerides Triglycerides Fatty Acids and Lipids from chylomicrons (loss of lipoprotein lipase Lipoprotein lipase An enzyme of the hydrolase class that catalyzes the reaction of triacylglycerol and water to yield diacylglycerol and a fatty acid anion. The enzyme hydrolyzes triacylglycerols in chylomicrons, very-low-density lipoproteins, low-density lipoproteins, and diacylglycerols. It occurs on capillary endothelial surfaces, especially in mammary, muscle, and adipose tissue. Lipid Metabolism (LPL))
  • Mutation Mutation Genetic mutations are errors in DNA that can cause protein misfolding and dysfunction. There are various types of mutations, including chromosomal, point, frameshift, and expansion mutations. Types of Mutations in proprotein convertase subtilisin/kexin type 9 (PCSK9, a serine Serine A non-essential amino acid occurring in natural form as the l-isomer. It is synthesized from glycine or threonine. It is involved in the biosynthesis of purines; pyrimidines; and other amino acids. Synthesis of Nonessential Amino Acids protease Protease Enzyme of the human immunodeficiency virus that is required for post-translational cleavage of gag and gag-pol precursor polyproteins into functional products needed for viral assembly. HIV protease is an aspartic protease encoded by the amino terminus of the pol gene. HIV Infection and AIDS) causes decreased 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 → decreased clearance of LDL by 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 → hypercholesterolemia
  • Dyslipidemia is a major risk factor for CAD.
  • Chronic HLD (hypercholesterolemia) directly impairs endothelial function due to increased local free radical Free Radical Highly reactive molecules with an unsatisfied electron valence pair. Free radicals are produced in both normal and pathological processes. They are proven or suspected agents of tissue damage in a wide variety of circumstances including radiation, damage from environment chemicals, and aging. Natural and pharmacological prevention of free radical damage is being actively investigated. Nitroimidazoles production.
  • Lp accumulation within the vascular (arterial, arteriolar) intima stimulates 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 through oxidized LDL and 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 crystals ( foam cells Foam cells Lipid-laden macrophages originating from monocytes or from smooth muscle cells. Atherosclerosis).
  • Both of these processes are pathogenic steps in 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 and Classification

Etiology

Causes of dyslipidemia can be divided into primary (familial) and secondary (acquired) causes.

Primary causes: 

  • Polygenic inheritance
  • 5 subtypes of dyslipidemias classified according to the Fredrickson phenotype Phenotype The complete genetic complement contained in the DNA of a set of chromosomes in a human. The length of the human genome is about 3 billion base pairs. Basic Terms of Genetics

Secondary (acquired) causes:

  • Lifestyle:
    • 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
    • Cigarette smoking Smoking Willful or deliberate act of inhaling and exhaling smoke from burning substances or agents held by hand. Interstitial Lung Diseases
    • Heavy alcohol use
  • Systemic Illness:
    • Diabetes mellitus Diabetes mellitus 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
      • HLD is associated with insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin resistance Resistance Physiologically, the opposition to flow of air caused by the forces of friction. As a part of pulmonary function testing, it is the ratio of driving pressure to the rate of air flow. Ventilation: Mechanics of Breathing.
      • Hypertriglyceridemia, low HDL, and high LDL
    • Cholestatic 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
    • 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:
      • Decreased plasma Plasma The residual portion of blood that is left after removal of blood cells by centrifugation without prior blood coagulation. Transfusion Products oncotic pressure Oncotic Pressure Edema
      • Induced 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 production of Lps
      • Elevated total and 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  
    • Chronic 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
    • 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 
    • Depression
    • Psoriasis Psoriasis Psoriasis is a common T-cell-mediated inflammatory skin condition. The etiology is unknown, but is thought to be due to genetic inheritance and environmental triggers. There are 4 major subtypes, with the most common form being chronic plaque psoriasis. Psoriasis
  • Medications:
    • Thiazide Thiazide Heterocyclic compounds with sulfur and nitrogen in the ring. This term commonly refers to the benzothiadiazines that inhibit sodium-potassium-chloride symporters and are used as diuretics. Hyponatremia diuretics Diuretics Agents that promote the excretion of urine through their effects on kidney function. Heart Failure and Angina Medication
    • Beta-blockers Beta-blockers Drugs that bind to but do not activate beta-adrenergic receptors thereby blocking the actions of beta-adrenergic agonists. Adrenergic beta-antagonists are used for treatment of hypertension, cardiac arrhythmias, angina pectoris, glaucoma, migraine headaches, and anxiety. Class 2 Antiarrhythmic Drugs (Beta Blockers)
    • Oral estrogens
    • Protease Protease Enzyme of the human immunodeficiency virus that is required for post-translational cleavage of gag and gag-pol precursor polyproteins into functional products needed for viral assembly. HIV protease is an aspartic protease encoded by the amino terminus of the pol gene. HIV Infection and AIDS inhibitors

Fredrickson classification for inherited dyslipoproteinemia

Table: Fredrickson classification for inherited dyslipoproteinemia (DLP
Type Condition, mode of inheritance ( 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 ( AD AD The term advance directive (AD) refers to treatment preferences and/or the designation of a surrogate decision-maker in the event that a person becomes unable to make medical decisions on their own behalf. Advance directives represent the ethical principle of autonomy and may take the form of a living will, health care proxy, durable power of attorney for health care, and/or a physician’s order for life-sustaining treatment. Advance Directives), autosomal recessive Autosomal recessive Autosomal inheritance, both dominant and recessive, refers to the transmission of genes from the 22 autosomal chromosomes. Autosomal recessive diseases are only expressed when 2 copies of the recessive allele are inherited. Autosomal Recessive and Autosomal Dominant Inheritance ( AR AR Aortic regurgitation (AR) is a cardiac condition characterized by the backflow of blood from the aorta to the left ventricle during diastole. Aortic regurgitation is associated with an abnormal aortic valve and/or aortic root stemming from multiple causes, commonly rheumatic heart disease as well as congenital and degenerative valvular disorders. Aortic Regurgitation)), lipid abnormality Pathology Notes
I Familial hyperchylomicronemia ( AR AR Aortic regurgitation (AR) is a cardiac condition characterized by the backflow of blood from the aorta to the left ventricle during diastole. Aortic regurgitation is associated with an abnormal aortic valve and/or aortic root stemming from multiple causes, commonly rheumatic heart disease as well as congenital and degenerative valvular disorders. Aortic Regurgitation)
Elevated chylomicrons
Deficiency in LPL or apolipoprotein C-II (ApoC-II)
  • Very high triglyceride levels (> 1,000 mg/dL)
  • No increased risk 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
IIa Familial hypercholesterolemia (FH) ( AD AD The term advance directive (AD) refers to treatment preferences and/or the designation of a surrogate decision-maker in the event that a person becomes unable to make medical decisions on their own behalf. Advance directives represent the ethical principle of autonomy and may take the form of a living will, health care proxy, durable power of attorney for health care, and/or a physician’s order for life-sustaining treatment. Advance Directives)
Elevated LDL
Mutation Mutation Genetic mutations are errors in DNA that can cause protein misfolding and dysfunction. There are various types of mutations, including chromosomal, point, frameshift, and expansion mutations. Types of Mutations in PCSK-9, defective 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 or apolipoprotein B-100 (ApoB-100)
  • High 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
  • Normal triglyceride levels
  • Responsible for 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 CAD
IIb Familial combined hypercholesterolemia ( AD AD The term advance directive (AD) refers to treatment preferences and/or the designation of a surrogate decision-maker in the event that a person becomes unable to make medical decisions on their own behalf. Advance directives represent the ethical principle of autonomy and may take the form of a living will, health care proxy, durable power of attorney for health care, and/or a physician’s order for life-sustaining treatment. Advance Directives)
Elevated VLDL and LDL
  • Massively 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
  • Responsible for 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 CAD
III Familial hyperlipoproteinemia ( AR AR Aortic regurgitation (AR) is a cardiac condition characterized by the backflow of blood from the aorta to the left ventricle during diastole. Aortic regurgitation is associated with an abnormal aortic valve and/or aortic root stemming from multiple causes, commonly rheumatic heart disease as well as congenital and degenerative valvular disorders. Aortic Regurgitation)
Remnants of VLDL and chylomicrons
Defective ApoE
  • Elevated triglyceride and 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
  • Responsible for 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 CAD
IV Familial hypertriglyceridemia ( AD AD The term advance directive (AD) refers to treatment preferences and/or the designation of a surrogate decision-maker in the event that a person becomes unable to make medical decisions on their own behalf. Advance directives represent the ethical principle of autonomy and may take the form of a living will, health care proxy, durable power of attorney for health care, and/or a physician’s order for life-sustaining treatment. Advance Directives)
Elevated VLDL
Excessive VLDL production by 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
  • Massively increased triglyceride levels
  • Responsible for 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 CAD
V Mixed HLD ( AR AR Aortic regurgitation (AR) is a cardiac condition characterized by the backflow of blood from the aorta to the left ventricle during diastole. Aortic regurgitation is associated with an abnormal aortic valve and/or aortic root stemming from multiple causes, commonly rheumatic heart disease as well as congenital and degenerative valvular disorders. Aortic Regurgitation)
Elevated chylomicrons and VLDL
Defective apolipoprotein A5 (ApoA5)
  • Massively elevated triglyceride levels
  • No increased risk 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

Clinical Presentation

  • Due to an increased 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, the majority of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship present with the following:
    • 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)
    • CAD
    • MI MI 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
  • High levels of triglycerides Triglycerides Fatty Acids and Lipids may also cause pancreatitis Pancreatitis Inflammation of the pancreas. Pancreatitis is classified as acute unless there are computed tomographic or endoscopic retrograde cholangiopancreatographic findings of chronic pancreatitis. The two most common forms of acute pancreatitis are alcoholic pancreatitis and gallstone pancreatitis. Acute Pancreatitis or fatty 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.
  • Clinical examination may reveal the following (usually indicative of an underlying primary cause):
    • Xanthomas: lipid deposits on 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
      • Tendon xanthomata: most commonly on the Achilles tendon and dorsum of hands 
      • Plantar xanthomas: occurs on palms and soles
    • Xanthelasmas: 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 plaques on the inner, upper eyelid
    • Arcus lipoides corneae: 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 deposition on cornea Cornea The transparent anterior portion of the fibrous coat of the eye consisting of five layers: stratified squamous corneal epithelium; bowman membrane; corneal stroma; descemet membrane; and mesenchymal corneal endothelium. It serves as the first refracting medium of the eye. Eye: Anatomy, resulting in yellow discoloration

Diagnosis and Management

Diagnosis

  • Indications for screening Screening Preoperative Care:
  • Diagnostic tests Diagnostic tests Diagnostic tests are important aspects in making a diagnosis. Some of the most important epidemiological values of diagnostic tests include sensitivity and specificity, false positives and false negatives, positive and negative predictive values, likelihood ratios, and pre-test and post-test probabilities. Epidemiological Values of Diagnostic Tests:
    • Fasting lipid profile (preferred):
    • Investigate for secondary causes in younger patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship ( 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, thyroid-stimulating hormone Thyroid-stimulating hormone A glycoprotein hormone secreted by the adenohypophysis. Thyrotropin stimulates thyroid gland by increasing the iodide transport, synthesis and release of thyroid hormones (thyroxine and triiodothyronine). Thyroid Hormones (TSH), 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, etc ETC The electron transport chain (ETC) sends electrons through a series of proteins, which generate an electrochemical proton gradient that produces energy in the form of adenosine triphosphate (ATP). Electron Transport Chain (ETC).)
    • Calculate Framingham risk score (risk for developing a cardiovascular event in the following 10 years)
    • Genetic testing Genetic Testing Detection of a mutation; genotype; karyotype; or specific alleles associated with genetic traits, heritable diseases, or predisposition to a disease, or that may lead to the disease in descendants. It includes prenatal genetic testing. Myotonic Dystrophies may be done to confirm FH.
Table: Normal values of lipids Lipids Lipids are a diverse group of hydrophobic organic molecules, which include fats, oils, sterols, and waxes. Fatty Acids and Lipids in blood
Lipid Normal value
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 < 200 mg/dL
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 > 60 mg/dL
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 < 100 mg/dL
Triglycerides Triglycerides Fatty Acids and Lipids < 150 mg/dL
Friedewald formula: LDL= 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 – HDL – ( triglycerides Triglycerides Fatty Acids and Lipids/5)

Management

The aim of management is to reduce the risk of cardiovascular diseases.

  • Encourage lifestyle modifications for all patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship.
  • Lifestyle modifications include:
    • Diet management and weight loss Weight loss Decrease in existing body weight. Bariatric Surgery
    • Smoking Smoking Willful or deliberate act of inhaling and exhaling smoke from burning substances or agents held by hand. Interstitial Lung Diseases cessation
    • Decreased alcohol intake
    • Optimal physical activity 
    • Blood pressure management
      • Goal for the general population: < 140/90 mm MM Multiple myeloma (MM) is a malignant condition of plasma cells (activated B lymphocytes) primarily seen in the elderly. Monoclonal proliferation of plasma cells results in cytokine-driven osteoclastic activity and excessive secretion of IgG antibodies. Multiple Myeloma Hg
      • Goal for individuals with risk >10%: < 130/80 mm MM Multiple myeloma (MM) is a malignant condition of plasma cells (activated B lymphocytes) primarily seen in the elderly. Monoclonal proliferation of plasma cells results in cytokine-driven osteoclastic activity and excessive secretion of IgG antibodies. Multiple Myeloma Hg
  • Pharmacological approach:
    • Statins are the 1st line of therapy; the intensity varies based on LDL levels and Framingham risk.
    • Statin examples:
      • 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 (Lipitor)
      • Lovastatin Lovastatin A fungal metabolite isolated from cultures of aspergillus terreus. The compound is a potent anticholesteremic agent. It inhibits 3-hydroxy-3-methylglutaryl coenzyme a reductase, which is the rate-limiting enzyme in cholesterol biosynthesis. It also stimulates the production of low-density lipoprotein receptors in the liver. Statins (Altoprev)
      • Pitavastatin Pitavastatin Statins (Livalo, Zypitamag)
      • Pravastatin Pravastatin An antilipemic fungal metabolite isolated from cultures of nocardia autotrophica. It acts as a competitive inhibitor of hmg CoA reductase. Statins (Pravachol)
      • 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 (Crestor, Ezallor)
      • Simvastatin Simvastatin A derivative of lovastatin and potent competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme a reductase, which is the rate-limiting enzyme in cholesterol biosynthesis. It may also interfere with steroid hormone production. Due to the induction of hepatic ldl receptors, it increases breakdown of ldl cholesterol. Statins (Zocor)

References

  1. Kaiser Permanente. (2020). Atherosclerotic Cardiovascular Disease Guidelines. https://wa.kaiserpermanente.org/static/pdf/public/guidelines/ascvd-primary.pdf
  2. Robertson, RS. (2021). Measurement of blood lipids and lipoproteins. UpToDate. Retrieved September 27, 2021, from https://www.uptodate.com/contents/measurement-of-blood-lipids-and-lipoproteins?search=cholesterol&topicRef=4565&source=see_link#H24361294
  3. Robertson, RS. (2021). Secondary causes of dyslipidemia. UpToDate. Retrieved September 27, 2021, from https://www.uptodate.com/contents/secondary-causes-of-dyslipidemia?search=dyslipidemia&source=search_result&selectedTitle=7~150&usage_type=default&display_rank=6#H2

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