Lipid Disorders (Clinical)

Overview

Definition^[17]

Dyslipidemia: abnormal amounts of 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 

• 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 atherogenic 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 (LDL, VLDL)
• 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:
  • 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 (TC) ≥ 240 mg/dL
  • Borderline high = 200–239 mg/dL
• Hypertriglyceridemia Hypertriglyceridemia A condition of elevated levels of triglycerides in the blood. Lipid Disorders: > 150 mg/dL

Epidemiology^[20]

• 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.
• In the US, about 11.3 % of adults (≥ 20 years of age) have 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 > 240 mg/dL.
• About 13.8 % have low HDL levels (< 40 mg/dL), a risk factor for ASCVD.
• Family history Family History Adult Health Maintenance 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 ASCVD is common and is a risk-enhancing factor.
• Familial hypercholesterolemia Familial hypercholesterolemia Lipid Disorders is a common genetic disorder, affecting 1:250 individuals worldwide.

Pathophysiology^[17]

• 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 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 (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 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
• Dyslipidemia is a major risk factor for CAD.
  • Chronic hyperlipidemia ( 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) 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) 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

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 are due to a combination of diet and lifestyle habits coupled with a genetic predisposition.

Etiology^[3,17,25]

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

Primary causes: 

• Can be from monogenic disorders (due to single gene Gene 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. Basic Terms of Genetics defects) or polygenic defects leading to a particular 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; examples include:
  • Familial hypercholesterolemia Familial hypercholesterolemia Lipid Disorders (FH):
    • 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 of 1 or more 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 involved in LDL-C catabolism (involving 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, APOB, PCSK9)
    • Extremely elevated LDL-C
    • Increased 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 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 (CHD)
  • Familial combined hyperlipidemia (FCHL)
    • 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, LDL-C, triglycerides Triglycerides Fatty Acids and Lipids and apolipoprotein (apo) B
    • Increased 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 CHD
  • Polygenic 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
    • Elevated LDL-C but not as marked as FH
    • Multiple gene Gene 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. Basic Terms of Genetics variants
    • Increased 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 CHD
  • Familial dysbetalipoproteinemia
    • 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 and triglycerides Triglycerides Fatty Acids and Lipids
    • 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 of the apolipoprotein E (APOE) gene Gene 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. Basic Terms of Genetics
    • Increased 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 CHD
  • Familial hyperapobetalipoproteinemia
    • Elevated apoB
    • LDL-C/apoB ratio < 1.2
    • Increased 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 CHD
• The subtypes of dyslipidemias Dyslipidemias Abnormalities in the serum levels of lipids, including overproduction or deficiency. Abnormal serum lipid profiles may include high total cholesterol, high triglycerides, low high density lipoprotein cholesterol, and elevated low density lipoprotein cholesterol. Lipid Disorders were historically 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 (see table)
  •  Abnormalities include 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 ( 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, Fredrickson Class IIa), elevated triglycerides Triglycerides Fatty Acids and Lipids ( hypertriglyceridemia Hypertriglyceridemia A condition of elevated levels of triglycerides in the blood. Lipid Disorders, Frederickson Classes I, IV and V), or a combination of the two (Fredrickson Classes III or IIb).
  • Not widely used due to better characterization of the genetic defect Genetic Defect Ion Channel Myopathy in dyslipidemias Dyslipidemias Abnormalities in the serum levels of lipids, including overproduction or deficiency. Abnormal serum lipid profiles may include high total cholesterol, high triglycerides, low high density lipoprotein cholesterol, and elevated low density lipoprotein cholesterol. Lipid Disorders

Secondary (acquired) causes:

• Hyperlipidemia due to an underlying etiology separate from a primary 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^[16]
• 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
• Diseases:
  • 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:
    • Hyperlipidemia is associated with insulin resistance Insulin resistance Diminished effectiveness of insulin in lowering blood sugar levels: requiring the use of 200 units or more of insulin per day to prevent hyperglycemia or ketosis. Diabetes Mellitus.
    • Hypertriglyceridemia Hypertriglyceridemia A condition of elevated levels of triglycerides in the blood. Lipid Disorders, 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 
  • Chronic inflammatory disease
• 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: increased triglycerides Triglycerides Fatty Acids and Lipids (can be severe in predisposed patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship)
• 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 Chronic Coronary Syndrome 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) (nonselective)
  • Oral estrogens
  • Protease inhibitors Protease Inhibitors Compounds which inhibit or antagonize biosynthesis or actions of proteases (endopeptidases). Anti-HIV Drugs
  • Atypical antipsychotics Atypical Antipsychotics Antiemetics (e.g., olanzapine Olanzapine A benzodiazepine derivative that binds serotonin receptors; muscarinic receptors; histamine h1 receptors; adrenergic alpha-1 receptors; and dopamine receptors. It is an antipsychotic agent used in the treatment of schizophrenia; bipolar disorder; and major depressive disorder; it may also reduce nausea and vomiting in patients undergoing chemotherapy. Second-Generation Antipsychotics)
  • Immunosuppressants Immunosuppressants Immunosuppressants are a class of drugs widely used in the management of autoimmune conditions and organ transplant rejection. The general effect is dampening of the immune response. Immunosuppressants (e.g., tacrolimus Tacrolimus A macrolide isolated from the culture broth of a strain of streptomyces tsukubaensis that has strong immunosuppressive activity in vivo and prevents the activation of T-lymphocytes in response to antigenic or mitogenic stimulation in vitro. Immunosuppressants)

Clinical Presentation

Many individuals with hyperlipidemia and hypertriglyceridemia Hypertriglyceridemia A condition of elevated levels of triglycerides in the blood. Lipid Disorders are asymptomatic, without symptoms and signs (other than those listed below). The most common clinical manifestation 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 is ASCVD.^[17,23]

• People with homozygous familial hypercholesterolemia Familial hypercholesterolemia Lipid Disorders may present with consequences 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 ASCVD while very young (< age 20).
• Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with heterozygous familial hyperlipidemia may present with:
  • 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 or angina
  • 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 or sudden cardiac death Sudden cardiac death Cardiac arrest is the sudden, complete cessation of cardiac output with hemodynamic collapse. Patients present as pulseless, unresponsive, and apneic. Rhythms associated with cardiac arrest are ventricular fibrillation/tachycardia, asystole, or pulseless electrical activity. Cardiac Arrest
  • Stroke
  • Coronary artery Coronary Artery Truncus Arteriosus calcification can be identified between ages 11 and 23.
• 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 Xanthomas Lipid Disorders: 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 Xanthomas Lipid Disorders: occurs on palms and soles
  • Xanthelasmas Xanthelasmas Lipid Disorders: 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
  • 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 or 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:
    • 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 in younger individuals (< age 45) with familial hyperlipidemia
    • Associated with an increased risk of heart disease in people with familial hyperlipidemia
    • Not related to hyperlipidemia when seen in older adults (> age 45)

Diagnosis

Dyslipidemia is defined as lipid values associated with an increased risk of and/or presence of disease for which the initiation of lipid-lowering therapy will be of benefit. There is controversy regarding the age at which to start screening Screening Preoperative Care, and guidelines for children and young adults vary. The recommendations listed below are based on the American Heart Association American Heart Association A voluntary organization concerned with the prevention and treatment of heart and vascular diseases. Heart Failure guidelines.

Lipid screening Screening Preoperative Care^[8,13]

• Screen individuals between 40 and 75 years of age.
• No recommendations for or against screening Screening Preoperative Care for dyslipidemia in individuals < 35 years of age
• Nonfasting screening Screening Preoperative Care for 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 and HDL in men ≥ 35 and women ≥ 45
• Screen and treat men ages 20–35 and women 20–45 if they have increased risk factors for cardiovascular disease:
  • 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
  • Smoking Smoking Willful or deliberate act of inhaling and exhaling smoke from burning substances or agents held by hand. Interstitial Lung Diseases
  • 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
  • Family history Family History Adult Health Maintenance of cardiovascular disease in 1st-degree male family members < age 50 and 1st-degree female family members < age 60
• Baseline lipid testing in young adults is also recommended at initiation of care with an adult primary care provider.
  • Repeat screening Screening Preoperative Care is guided by the patient’s cardiovascular disease risk.
  • Assessment of cardiovascular disease risk and lipid levels are recommended to be repeated:
    • Generally, every 5 years 
    • Every 3 years if near the threshold Threshold Minimum voltage necessary to generate an action potential (an all-or-none response) Skeletal Muscle Contraction for treatment

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^[2,4,8,17]

• Fasting lipid profile Lipid profile Lipid Disorders (preferred for screening Screening Preoperative Care):
  • 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 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 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 (TGs)
• Other lipid measurements:
  • Apolipoprotein B (apoB) and lipoprotein (a) (Lp(a)):
    • Can be considered risk-enhancing factors for ASCVD
    • Some studies show an association between apoB and ASCVD; others report correlation Correlation Determination of whether or not two variables are correlated. This means to study whether an increase or decrease in one variable corresponds to an increase or decrease in the other variable. Causality, Validity, and Reliability between apoB and 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.
    • Lp(a): modified form of LDL with atherogenic potential
  • ApoB levels: may be helpful for individuals with significant hypertriglyceridemia Hypertriglyceridemia A condition of elevated levels of triglycerides in the blood. Lipid Disorders
    • ApoB > 130 mg/dL corresponds to an LDL ≥ 160 mg/dL.
    • Expense and lack of reliability Reliability Reliability refers to the reproducibility of a test or research finding. Causality, Validity, and Reliability of testing makes this test nonstandard.
  • Lp(a) relative indications:
    • Family history Family History Adult Health Maintenance 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 ASCVD
    • Personal history of ASCVD not explained by major risk factors
• 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:
  • HbA_1c
  • 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 
  • 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
• Calculate 10-year ASCVD risk (risk for developing a cardiovascular event in the following 10 years): AHA/ACC calculator (for age 40–75)
• 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.

Billing and Coding

Diagnosis Codes:

These codes are used to diagnose various types of dyslipidemia, or abnormal amounts of 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. The codes specify the type of lipid that is elevated, such as pure 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 (high 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), hypertriglyceridemia Hypertriglyceridemia A condition of elevated levels of triglycerides in the blood. Lipid Disorders (high triglycerides Triglycerides Fatty Acids and Lipids), or mixed hyperlipidemia Mixed Hyperlipidemia Lipid Disorders (both are high).

Evaluation & Workup:

This CPT code is for a standard fasting lipid panel, the essential blood test to diagnose and monitor 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. It measures 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, 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) 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, 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, and triglycerides Triglycerides Fatty Acids and Lipids.

Medications:

These codes are for the primary classes of medications used to treat 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. 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 the first-line therapy for 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, while fibrates Fibrates Lipid Control Drugs are often used for very high triglycerides Triglycerides Fatty Acids and Lipids.

Complications:

These codes are used to document the major long-term consequences of untreated hyperlipidemia, which are primarily manifestations 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. This includes coronary artery Coronary Artery Truncus Arteriosus disease, heart attacks ( 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 ischemic strokes.