Lipid Disorders (Clinical)

Management

The aim of management is to reduce the risk of cardiovascular disease including heart attack Heart attack 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.^[8]

• Clinical trials show that lowering LDL reduces ASCVD risk:
  • Meta-analysis: ↓ LDL by 38.7 mg/dL → 21% reduction in ASCVD risk
  • Responses to statin therapy depend on baseline concentration.
• 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.

Diet management^[9]

• Ask about dietary habits in regular Regular Insulin medical visits: utilize evidence-based heart-healthy foods for improving cardiometabolic risk factors, dyslipidemia, and ASCVD risk.
• Follow ACC/AHA diet recommendations for ASCVD prevention and lipid reduction:^[5,22]
  • Limit Limit A value (e.g., pressure or time) that should not be exceeded and which is specified by the operator to protect the lung Invasive Mechanical Ventilation saturated fatty acids Saturated fatty acids Fatty Acids and Lipids and trans fatty acids Acids Chemical compounds which yield hydrogen ions or protons when dissolved in water, whose hydrogen can be replaced by metals or basic radicals, or which react with bases to form salts and water (neutralization). An extension of the term includes substances dissolved in media other than water. Acid-Base Balance.
  • Eat diet rich in fresh (unprocessed) fruits and vegetables.
  • Manage overweight/ 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 with calorie reduction and regular Regular Insulin exercise.
• Include National Lipid Association (NLA) nutrition goals for optimizing LDL, 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, and TG Tg Thyroid Hormones levels.^[8]
• Dietary adjuncts:
  • Fiber supplements
  • Plant sterols Sterols 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. Fatty Acids and Lipids (phytosterols) 

Other cardiovascular risk factor assessment and management^[8]

• 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 Hg
  • Goal for individuals with risk >10%: < 130/80 mm Hg
• Screen for 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 per guidelines:^[10,24]
  • USPSTF: adults ages 35‒70 years with a BMI BMI An indicator of body density as determined by the relationship of body weight to body height. Bmi=weight (kg)/height squared (m2). Bmi correlates with body fat (adipose tissue). Their relationship varies with age and gender. For adults, bmi falls into these categories: below 18. 5 (underweight); 18. 5-24. 9 (normal); 25. 0-29. 9 (overweight); 30. 0 and above (obese). Obesity ≥ 25
  • American 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 Association ( ADA ADA An enzyme that catalyzes the hydrolysis of adenosine to inosine with the elimination of ammonia. Purine and Pyrimidine Metabolism):
    • Screen all adults ≥ 35 years of age.
    • Consider screening Screening Preoperative Care adults of any age with overweight or 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 ( BMI BMI An indicator of body density as determined by the relationship of body weight to body height. Bmi=weight (kg)/height squared (m2). Bmi correlates with body fat (adipose tissue). Their relationship varies with age and gender. For adults, bmi falls into these categories: below 18. 5 (underweight); 18. 5-24. 9 (normal); 25. 0-29. 9 (overweight); 30. 0 and above (obese). Obesity ≥ 25 (≥ 23 in Asian Americans)) who have ≥ 1 risk factors (e.g., 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, HDL < 35 mg/dL).

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 for primary prevention^[1,5,8,14]

• Calculate the patient’s ASCVD risk as a percentage based on:
  • Age
  • Systolic BP
  • 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 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
  • 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 on medications
  • Cigarette smoking Smoking Willful or deliberate act of inhaling and exhaling smoke from burning substances or agents held by hand. Interstitial Lung 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
• Risk calculators:
  • US: ASCVD risk calculator 
  • UK: QRISK3 assessment tool
• US: American Heart Association American Heart Association A voluntary organization concerned with the prevention and treatment of heart and vascular diseases. Heart Failure/American College of Cardiology (AHA/ACC) 2018 recommendations:^[5,8]
  • In adults < 40 years of age:
    • Advised to estimate lifetime risk 
    • Statin therapy is recommended only for selected patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with moderately high LDL (≥ 160 mg/dL) or very high LDL (≥ 190 mg/dL). 
  • 3 high-risk categories for which statin therapy is recommended:
    • Severe 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 LDL (≥ 190 mg/dL): no risk scoring required
    • Adults ages 40‒75 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 mellitus
    • Adults ages 40‒75 with LDL ≥ 70 mg/dL and a 10-year ASCVD risk > 7.5%
• UK: National Institute for Health and Care Excellence (NICE) recommendations:^[14]
  • Adults ≤ 84 years with ≥ 10% 10-year ASCVD risk
  • Adults > 84 years may also benefit, but decision should consider:
    • Patient preference
    • Life expectancy Life expectancy Based on known statistical data, the number of years which any person of a given age may reasonably expected to live. Population Pyramids and frailty
    • Polypharmacy
    • 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
• Check baseline 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 transaminase Transaminase A subclass of enzymes of the transferase class that catalyze the transfer of an amino group from a donor (generally an amino acid) to an acceptor (generally a 2-keto acid). Most of these enzymes are pyridoxyl phosphate proteins. Catabolism of Amino Acids levels before starting 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.

Lipid-lowering medications— 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^[8,21]

• Choice depends on:
  • Degree of hyperlipidemia and ASCVD risk:
    • High-intensity therapy: lowers LDL by about ≥ 50%
    • Moderate-intensity: lowers LDL 30%–49% (start most patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship here)
    • Low-intensity: lowers LDL by < 30%
    • Varies in clinical practice
  • Drug interactions
  • Comorbid CKD CKD Chronic kidney disease (CKD) is kidney impairment that lasts for ≥ 3 months, implying that it is irreversible. Hypertension and diabetes are the most common causes; however, there are a multitude of other etiologies. In the early to moderate stages, CKD is usually asymptomatic and is primarily diagnosed by laboratory abnormalities. Chronic Kidney Disease ( 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 or fluvastatin Fluvastatin An indole-heptanoic acid derivative that inhibits hmg CoA reductase and is used to treat hypercholesterolemia. In contrast to other statins, it does not appear to interact with other drugs that inhibit cyp3a4. Statins preferred; no dose adjustment needed)
  • Cost
• Potential adverse 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:^[6]
  • Myalgias Myalgias Painful sensation in the muscles. Tick-borne Encephalitis Virus: usually leg Leg The lower leg, or just “leg” in anatomical terms, is the part of the lower limb between the knee and the ankle joint. The bony structure is composed of the tibia and fibula bones, and the muscles of the leg are grouped into the anterior, lateral, and posterior compartments by extensions of fascia. Leg: Anatomy cramps Cramps Ion Channel Myopathy; not associated with an elevation in CK
    • Symptoms temporally related to status without known causality Causality Causality is a relationship between 2 events in which 1 event causes the other. Simply because relationships are observed between 2 variables (i.e., associations or correlations) does not imply that one variable actually caused the outcome. Demonstrating causality between an exposure and an outcome is the main objective of most published medical research. Causality, Validity, and Reliability (5%–25%)
    • Muscle symptoms due to pharmacologic properties of the statin (0.5%–4%)
  • Rare myonecrosis Myonecrosis A severe condition resulting from bacteria invading healthy muscle from adjacent traumatized muscle or soft tissue. The infection originates in a wound contaminated with bacteria of the genus Clostridium. C. perfringens accounts for the majority of cases (over eighty percent), while C. novyi, C. septicum, and C. histolyticum cause most of the other cases. Clostridia (0.5%) and rhabdomyolysis Rhabdomyolysis Rhabdomyolysis is characterized by muscle necrosis and the release of toxic intracellular contents, especially myoglobin, into the circulation. Rhabdomyolysis (< 0.1%) 
  • 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 dysfunction
• 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 statin-associated myopathy Myopathy Dermatomyositis:
  • Acute or chronic renal failure Renal failure Conditions in which the kidneys perform below the normal level in the ability to remove wastes, concentrate urine, and maintain electrolyte balance; blood pressure; and calcium metabolism. Renal insufficiency can be classified by the degree of kidney damage (as measured by the level of proteinuria) and reduction in glomerular filtration rate. Crush Syndrome
  • Obstructive 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
  • Neuromuscular disorders
  • Concurrent drug therapy with a cytochrome P450 Cytochrome P450 A superfamily of hundreds of closely related hemeproteins found throughout the phylogenetic spectrum, from animals, plants, fungi, to bacteria. They include numerous complex monooxygenases (mixed function oxygenases). In animals, these p450 enzymes serve two major functions: (1) biosynthesis of steroids, fatty acids, and bile acids; (2) metabolism of endogenous and a wide variety of exogenous substrates, such as toxins and drugs (biotransformation). They are classified, according to their sequence similarities rather than functions, into cyp gene families (>40% homology) and subfamilies (>59% homology). For example, enzymes from the cyp1, cyp2, and cyp3 gene families are responsible for most drug metabolism. Drug-Induced Liver Injury 3A4 ( CYP3A4 CYP3A4 Class 3 Antiarrhythmic Drugs (Potassium Channel Blockers)) inhibitor
• Common drug interactions with 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:
  • Fibrates Fibrates Lipid Control Drugs: If combination therapy is needed, fenofibrate Fenofibrate An antilipemic agent which reduces both cholesterol and triglycerides in the blood. Lipid Control Drugs is preferred over gemfibrozil Gemfibrozil A lipid-regulating agent that lowers elevated serum lipids primarily by decreasing serum triglycerides with a variable reduction in total cholesterol. Lipid Control Drugs.
  • Risk of muscle injury is higher when a statin metabolized by CYP3A4 CYP3A4 Class 3 Antiarrhythmic Drugs (Potassium Channel Blockers) ( 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, 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, 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) is used with another substance that interferes with CYP3A4 CYP3A4 Class 3 Antiarrhythmic Drugs (Potassium Channel Blockers). 
  • Inhibitors of CYP3A4 CYP3A4 Class 3 Antiarrhythmic Drugs (Potassium Channel Blockers):
    • Clarithromycin Clarithromycin A semisynthetic macrolide antibiotic derived from erythromycin that is active against a variety of microorganisms. It can inhibit protein synthesis in bacteria by reversibly binding to the 50s ribosomal subunits. This inhibits the translocation of aminoacyl transfer-RNA and prevents peptide chain elongation. Macrolides and Ketolides
    • Grapefruit juice
    • Antifungals: ketoconazole Ketoconazole Broad spectrum antifungal agent used for long periods at high doses, especially in immunosuppressed patients. Azoles and itraconazole Itraconazole A triazole antifungal agent that inhibits cytochrome p-450-dependent enzymes required for ergosterol synthesis. Azoles
    • Antiviral Antiviral Antivirals for Hepatitis B protease inhibitors Protease Inhibitors Compounds which inhibit or antagonize biosynthesis or actions of proteases (endopeptidases). Anti-HIV Drugs used for HIV HIV Anti-HIV Drugs infection (e.g., nelfinavir Nelfinavir A potent HIV protease inhibitor. It is used in combination with other antiviral drugs in the treatment of HIV in both adults and children. Anti-HIV Drugs, saquinavir Saquinavir An HIV protease inhibitor which acts as an analog of an HIV protease cleavage site. It is a highly specific inhibitor of HIV-1 and HIV-2 proteases, and also inhibits cytochrome p-450 cyp3a. Anti-HIV Drugs, ritonavir Ritonavir An HIV protease inhibitor that works by interfering with the reproductive cycle of HIV. It also inhibits cytochrome p-450 cyp3a. Anti-HIV Drugs)
  • Inducers of CYP3A4 CYP3A4 Class 3 Antiarrhythmic Drugs (Potassium Channel Blockers):
    • Antiseizure drugs: phenytoin Phenytoin An anticonvulsant that is used to treat a wide variety of seizures. The mechanism of therapeutic action is not clear, although several cellular actions have been described including effects on ion channels, active transport, and general membrane stabilization. Phenytoin has been proposed for several other therapeutic uses, but its use has been limited by its many adverse effects and interactions with other drugs. First-Generation Anticonvulsant Drugs and carbamazepine Carbamazepine A dibenzazepine that acts as a sodium channel blocker. It is used as an anticonvulsant for the treatment of grand mal and psychomotor or focal seizures. It may also be used in the management of bipolar disorder, and has analgesic properties. First-Generation Anticonvulsant Drugs
    • Rifampin Rifampin A semisynthetic antibiotic produced from streptomyces mediterranei. It has a broad antibacterial spectrum, including activity against several forms of Mycobacterium. In susceptible organisms it inhibits dna-dependent RNA polymerase activity by forming a stable complex with the enzyme. It thus suppresses the initiation of RNA synthesis. Rifampin is bactericidal, and acts on both intracellular and extracellular organisms. Epiglottitis
    • St. John’s wort
• Contraindicated in 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
• 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:
  • Start with high-intensity therapy.
  • 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 added to a moderate-intensity statin results in greater LDL reduction than monotherapy. 
  • LDL apheresis may be needed.
• For statin-intolerant individuals:
  • Very high-risk (≥ 20% 10-year ASCVD risk and LDL > 160 mg/dL): Consider proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors.
  • All other patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship:
    • Nonstatin drugs are not routinely recommended for primary prevention (no prior ASCVD).
    • Continue lifestyle and diet modifications.
    • Consider antiplatelet therapy in higher-risk patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship (e.g., aspirin Aspirin The prototypical analgesic used in the treatment of mild to moderate pain. It has anti-inflammatory and antipyretic properties and acts as an inhibitor of cyclooxygenase which results in the inhibition of the biosynthesis of prostaglandins. Aspirin also inhibits platelet aggregation and is used in the prevention of arterial and venous thrombosis. Nonsteroidal Antiinflammatory Drugs (NSAIDs))

Lipid-lowering medications: others^[7]

• 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 in 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
  • 10 mg orally once daily
• PCSK9 antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins: Types and Functions: interfere with PCSK9, 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 that degrades 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, leading to ↑ 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
  • Alirocumab Alirocumab Lipid Control Drugs (subcutaneous injection):
    • Homozygous familial hypercholesterolemia Familial hypercholesterolemia Lipid Disorders: 150 mg every 2 weeks
    • Primary hyperlipidemia: 75 mg once every 2 weeks or 300 mg once every 4 weeks (maximum, 150 mg every 2 weeks)
  • Evolocumab Evolocumab Lipid Control Drugs (subcutaneous injection):
    • Homozygous familial hypercholesterolemia Familial hypercholesterolemia Lipid Disorders: 420 mg once monthly (maximum, 420 mg once every 2 weeks)
    • Primary hyperlipidemia: 140 mg every 2 weeks or 420 mg once monthly
• Bempedoic acid Bempedoic Acid Lipid Control Drugs:
  • Inhibits ATP-citrate lyase (enzyme in 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)
  • Can be combined with a statin or 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
  • Can increase uric acid Uric acid An oxidation product, via xanthine oxidase, of oxypurines such as xanthine and hypoxanthine. It is the final oxidation product of purine catabolism in humans and primates, whereas in most other mammals urate oxidase further oxidizes it to allantoin. Nephrolithiasis
  • 180 mg orally once daily
• Evinacumab:
  • Inhibits angiopoietin-like protein 3 (ANGPTL3)
  • Adjunctive treatment for homozygous familial hypercholesterolemia Familial hypercholesterolemia Lipid Disorders
  • 15 mg/kg IV every 4 weeks
• Fibrates Fibrates Lipid Control Drugs:
  • Not recommended to reduce LDL (or increase HDL) in the absence of elevated TGs
  • Show no benefit in cardiovascular outcomes
  • Include:
    • Gemfibrozil Gemfibrozil A lipid-regulating agent that lowers elevated serum lipids primarily by decreasing serum triglycerides with a variable reduction in total cholesterol. Lipid Control Drugs 600 mg orally twice a day
    •   Fenofibrate Fenofibrate An antilipemic agent which reduces both cholesterol and triglycerides in the blood. Lipid Control Drugs (dose varies by formulation)
• Volanesorsen:
  • Inhibitor of apolipoprotein C-III (APOC3), reducing TGs
  • Approved for use in Europe but not in the US.

Subsequent monitoring and ASCVD risk assessment Risk assessment The qualitative or quantitative estimation of the likelihood of adverse effects that may result from exposure to specified health hazards or from the absence of beneficial influences. Preoperative Care^[8,14]

• Monitoring:
  • Lipid:
    • 6 weeks after starting medication, evaluating the response to treatment
    • Assess adherence.
    • Ask about side effects.
  • 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 transaminase Transaminase A subclass of enzymes of the transferase class that catalyze the transfer of an amino group from a donor (generally an amino acid) to an acceptor (generally a 2-keto acid). Most of these enzymes are pyridoxyl phosphate proteins. Catabolism of Amino Acids 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:
    • Obtain baseline level prior to initiating a statin.
    • Repeat within 3 months and 12 months, unless clinically indicated.
  • Creatine Creatine An amino acid that occurs in vertebrate tissues and in urine. In muscle tissue, creatine generally occurs as phosphocreatine. Creatine is excreted as creatinine in the urine. Acute Kidney Injury kinase (CK):
    • Routine monitoring is not indicated. 
    • If patient reports generalized muscle pains, obtain CK prior to initiating statin.
    • Start statin at a lower dose if with increased CK but not 5x the upper limit Limit A value (e.g., pressure or time) that should not be exceeded and which is specified by the operator to protect the lung Invasive Mechanical Ventilation of normal (ULN); do not give statin if levels are 5x the ULN.
• Additional nonstatin lipid-lowering medication is not recommended for primary prevention in most patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship who are not at very high risk.
• Reassess ASCVD risk periodically, especially when there is a change in clinical status.

Specialist referral^[21]

• Registered dietitian/nutritionist
• Cardiology/lipid specialist:
  • If LDL apheresis is needed
  • Severe familial hypercholesterolemia Familial hypercholesterolemia Lipid Disorders
• UK:^[14]
  • 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 > 9.0 mmol/L (SI units) 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 > 7.5 mmol/L, even in the absence of a 1st‑degree 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 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.
  • TG Tg Thyroid Hormones > 20 mmol/L unrelated to excess alcohol or poor glycemic control