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Dyslipidemia posterior heel pain and stiffness that improves with rest. On paresthesia that radiates distally into the plantar foot surface. examination, there is usually tenderness of the Achilles ten- On examination, pain may be reproduced with nerve tapping don approximately 2 to 6 cm above the calcaneal insertion. and with provocative measures that compress the nerve Treatment includes activity modification, eccentric exercises (plantar flexion-inversion and dorsiflexion-eversion tests). (muscle lengthening in response to external resistance), and First-line treatment consists of activity modification, orthot- use of appropriate footwear. NSAIDs can be used for pain ics, NSAIDs, and neuromodulators. control. Achilles tendon rupture commonly occurs during strenu- Forefoot Pain ous activities, although it may occur spontaneously in the Morton neuroma (interdigital nerve injury) causes pain elderly or rarely with fluoroquinolone use. Patients usually between the metatarsal heads and the sensation of walking on have heel pain and may report hearing a “pop.” On examina- a pebble. First-line therapy consists of footwear modification tion, a tendon defect may be palpable; a lack of plantar flexion and padding. Glucocorticoid injections may provide tempo- with calf squeezing suggests complete rupture (sensitivity, rary relief. Interdigital nerve resection is reserved for those 93%; specificity, 96%) (Figure 21). Treatment is controversial who do not respond to conservative measures. and consists of surgery with immobilization or immobiliza- Hammertoe deformities (proximal interphalangeal joint tion alone. flexion deformity with distal interphalangeal joint extension Plantar fasciitis classically causes sharp, medial-inferior and extended or neutral position of the metatarsophalangeal heel pain with the first morning steps and after prolonged rest. joint) occur with constricting footwear and increasing age. Pain usually improves with further walking but may persist in Treatment includes footwear modification, padding, and pos- severe cases. On examination, the medial calcaneal tubercle is sibly surgery. frequently tender. Passive toe dorsiflexion with standing may Hallux or bunion deformity (lateral deviation of great toe reproduce pain (sensitivity, 32%; specificity, 100%). Treatment with medial bony deformity of uncertain etiology) can lead to includes weight loss, rest, calf/heel stretching, and arch sup- pain, osteoarthritis of the first metatarsophalangeal joint, ports (if pes planus is present). NSAIDs may be helpful for pain and overlying bursitis. Treatment includes orthotic devices, control. Patients should be counseled that resolution can be NSAIDs, and possibly surgery. expected but may take months. For recalcitrant cases, ultra- sonography, extracorporeal shockwave therapy, night splints, e Treatment of acute ankle sprain includes intermittent and glucocorticoid injections can be considered. Surgery is cryotherapy, a lace-up support or air stirrup brace reserved for patients who do not respond to these measures. combined with elastic compression wrapping, early mobilization with weight bearing as tolerated, and Midfoot Pain acetaminophen and oral or topical NSAIDs. Tarsal tunnel syndrome (posterior tibial nerve compression as it passes through the tarsal tunnel) causes posteromedial heel e Stress fracture most commonly occurs in the metatar- sals, tarsals, and calcaneus and is suggested by pain with percussion or pain with hopping ona single leg; radiography is first-line diagnostic testing but may fail

posterior heel pain and stiffness that improves with rest. On paresthesia that radiates distally into the plantar foot surface. examination, there is usually tenderness of the Achilles ten- On examination, pain may be reproduced with nerve tapping don approximately 2 to 6 cm above the calcaneal insertion. and with provocative measures that compress the nerve Treatment includes activity modification, eccentric exercises (plantar flexion-inversion and dorsiflexion-eversion tests). (muscle lengthening in response to external resistance), and First-line treatment consists of activity modification, orthot- use of appropriate footwear. NSAIDs can be used for pain ics, NSAIDs, and neuromodulators. control. Achilles tendon rupture commonly occurs during strenu- Forefoot Pain ous activities, although it may occur spontaneously in the Morton neuroma (interdigital nerve injury) causes pain elderly or rarely with fluoroquinolone use. Patients usually between the metatarsal heads and the sensation of walking on have heel pain and may report hearing a “pop.” On examina- a pebble. First-line therapy consists of footwear modification tion, a tendon defect may be palpable; a lack of plantar flexion and padding. Glucocorticoid injections may provide tempo- with calf squeezing suggests complete rupture (sensitivity, rary relief. Interdigital nerve resection is reserved for those 93%; specificity, 96%) (Figure 21). Treatment is controversial who do not respond to conservative measures. and consists of surgery with immobilization or immobiliza- Hammertoe deformities (proximal interphalangeal joint tion alone. flexion deformity with distal interphalangeal joint extension Plantar fasciitis classically causes sharp, medial-inferior and extended or neutral position of the metatarsophalangeal heel pain with the first morning steps and after prolonged rest. joint) occur with constricting footwear and increasing age. Pain usually improves with further walking but may persist in Treatment includes footwear modification, padding, and pos- severe cases. On examination, the medial calcaneal tubercle is sibly surgery. frequently tender. Passive toe dorsiflexion with standing may Hallux or bunion deformity (lateral deviation of great toe reproduce pain (sensitivity, 32%; specificity, 100%). Treatment with medial bony deformity of uncertain etiology) can lead to includes weight loss, rest, calf/heel stretching, and arch sup- pain, osteoarthritis of the first metatarsophalangeal joint, ports (if pes planus is present). NSAIDs may be helpful for pain and overlying bursitis. Treatment includes orthotic devices, control. Patients should be counseled that resolution can be NSAIDs, and possibly surgery. expected but may take months. For recalcitrant cases, ultra- sonography, extracorporeal shockwave therapy, night splints, e Treatment of acute ankle sprain includes intermittent and glucocorticoid injections can be considered. Surgery is cryotherapy, a lace-up support or air stirrup brace reserved for patients who do not respond to these measures. combined with elastic compression wrapping, early mobilization with weight bearing as tolerated, and Midfoot Pain acetaminophen and oral or topical NSAIDs. Tarsal tunnel syndrome (posterior tibial nerve compression as it passes through the tarsal tunnel) causes posteromedial heel e Stress fracture most commonly occurs in the metatar- sals, tarsals, and calcaneus and is suggested by pain with percussion or pain with hopping ona single leg; radiography is first-line diagnostic testing but may fail to reveal a fracture line.

posterior heel pain and stiffness that improves with rest. On paresthesia that radiates distally into the plantar foot surface. examination, there is usually tenderness of the Achilles ten- On examination, pain may be reproduced with nerve tapping don approximately 2 to 6 cm above the calcaneal insertion. and with provocative measures that compress the nerve Treatment includes activity modification, eccentric exercises (plantar flexion-inversion and dorsiflexion-eversion tests). (muscle lengthening in response to external resistance), and First-line treatment consists of activity modification, orthot- use of appropriate footwear. NSAIDs can be used for pain ics, NSAIDs, and neuromodulators. control. Achilles tendon rupture commonly occurs during strenu- Forefoot Pain ous activities, although it may occur spontaneously in the Morton neuroma (interdigital nerve injury) causes pain elderly or rarely with fluoroquinolone use. Patients usually between the metatarsal heads and the sensation of walking on have heel pain and may report hearing a “pop.” On examina- a pebble. First-line therapy consists of footwear modification tion, a tendon defect may be palpable; a lack of plantar flexion and padding. Glucocorticoid injections may provide tempo- with calf squeezing suggests complete rupture (sensitivity, rary relief. Interdigital nerve resection is reserved for those 93%; specificity, 96%) (Figure 21). Treatment is controversial who do not respond to conservative measures. and consists of surgery with immobilization or immobiliza- Hammertoe deformities (proximal interphalangeal joint tion alone. flexion deformity with distal interphalangeal joint extension Plantar fasciitis classically causes sharp, medial-inferior and extended or neutral position of the metatarsophalangeal heel pain with the first morning steps and after prolonged rest. joint) occur with constricting footwear and increasing age. Pain usually improves with further walking but may persist in Treatment includes footwear modification, padding, and pos- severe cases. On examination, the medial calcaneal tubercle is sibly surgery. frequently tender. Passive toe dorsiflexion with standing may Hallux or bunion deformity (lateral deviation of great toe reproduce pain (sensitivity, 32%; specificity, 100%). Treatment with medial bony deformity of uncertain etiology) can lead to includes weight loss, rest, calf/heel stretching, and arch sup- pain, osteoarthritis of the first metatarsophalangeal joint, ports (if pes planus is present). NSAIDs may be helpful for pain and overlying bursitis. Treatment includes orthotic devices, control. Patients should be counseled that resolution can be NSAIDs, and possibly surgery. expected but may take months. For recalcitrant cases, ultra- sonography, extracorporeal shockwave therapy, night splints, e Treatment of acute ankle sprain includes intermittent and glucocorticoid injections can be considered. Surgery is cryotherapy, a lace-up support or air stirrup brace reserved for patients who do not respond to these measures. combined with elastic compression wrapping, early mobilization with weight bearing as tolerated, and Midfoot Pain acetaminophen and oral or topical NSAIDs. Tarsal tunnel syndrome (posterior tibial nerve compression as it passes through the tarsal tunnel) causes posteromedial heel e Stress fracture most commonly occurs in the metatar- sals, tarsals, and calcaneus and is suggested by pain with percussion or pain with hopping ona single leg; radiography is first-line diagnostic testing but may fail to reveal a fracture line. e Plantar fasciitis classically causes sharp, medial-inferior heel pain with the first morning steps and after pro- longed rest; the medial calcaneal tubercle is frequently tender.

e Plantar fasciitis classically causes sharp, medial-inferior heel pain with the first morning steps and after pro- longed rest; the medial calcaneal tubercle is frequently tender. Dyslipidemia Evaluation of Lipid Levels Major guidelines differ in their recommendations regarding when to initiate screening for lipid disease in adults. The U.S. Preventive Services Task Force (USPSTF) recommends universal FIGURE 21. Thompson test. The patient is positioned in the prone position. _ lipid screening in adults aged 40 to 75 years to calculate risk for The examiner squeezes mid-calf and observes for plantar flexion of the foot. When atherosclerotic cardiovascular disease (ASCVD) using the the patient has an intact Achilles tendon, plantar flexion will occur. When there is a complete Achilles tendon rupture, no plantar flexion is observed. American Heart Association (AHA)/American College of Cardiology (ACC) Pooled Cohort Equations (https://tools.acc. Reproduced with permission from Davis MF, Davis PF, Ross DS. Expert Guide to Sports Medicine. Philadelphia, PA: American College of Physicians; 2005:401. ©2005, American College of Physicians. org/ASCVD-Risk-Estimator-Plus). The 2018 AHA/ACC Guideline

Dyslipidemia Evaluation of Lipid Levels Major guidelines differ in their recommendations regarding when to initiate screening for lipid disease in adults. The U.S. Preventive Services Task Force (USPSTF) recommends universal FIGURE 21. Thompson test. The patient is positioned in the prone position. _ lipid screening in adults aged 40 to 75 years to calculate risk for The examiner squeezes mid-calf and observes for plantar flexion of the foot. When atherosclerotic cardiovascular disease (ASCVD) using the the patient has an intact Achilles tendon, plantar flexion will occur. When there is a complete Achilles tendon rupture, no plantar flexion is observed. American Heart Association (AHA)/American College of Cardiology (ACC) Pooled Cohort Equations (https://tools.acc. Reproduced with permission from Davis MF, Davis PF, Ross DS. Expert Guide to Sports Medicine. Philadelphia, PA: American College of Physicians; 2005:401. ©2005, American College of Physicians. org/ASCVD-Risk-Estimator-Plus). The 2018 AHA/ACC Guideline 66

Dyslipidemia on the Management of Blood Cholesterol assigns a high priority Pharmacologic treatment to raise HDL cholesterol levels is not to the estimation of lifetime ASCVD risk in children, adoles- recommended. cents, and young adults and promotion of lifestyle risk reduc- tion across the age spectrum. e The U.S. Preventive Services Task Force recommends Lipid measurement also may be indicated to investigate for universal lipid screening in adults aged 40 to 75 years to familial hypercholesterolemia; to determine adherence to and calculate risk for atherosclerotic cardiovascular disease. effectiveness of therapy; and to evaluate for dyslipidemia in the presence of potential complications, such as pancreatitis. e The primary utility of LDL cholesterol measurement is to identify patients who will benefit from treatment LDL Cholesterol with statin therapy and to assess response to therapy.

on the Management of Blood Cholesterol assigns a high priority Pharmacologic treatment to raise HDL cholesterol levels is not to the estimation of lifetime ASCVD risk in children, adoles- recommended. cents, and young adults and promotion of lifestyle risk reduc- tion across the age spectrum. e The U.S. Preventive Services Task Force recommends Lipid measurement also may be indicated to investigate for universal lipid screening in adults aged 40 to 75 years to familial hypercholesterolemia; to determine adherence to and calculate risk for atherosclerotic cardiovascular disease. effectiveness of therapy; and to evaluate for dyslipidemia in the presence of potential complications, such as pancreatitis. e The primary utility of LDL cholesterol measurement is to identify patients who will benefit from treatment LDL Cholesterol with statin therapy and to assess response to therapy. The association between high LDL cholesterol levels and increased risk for ASCVD is widely accepted. Historically, cho- Management of Dyslipidemias lesterol treatment targeted specific LDL cholesterol goals Treatment with therapeutic lifestyle changes and pharmaco- because LDL cholesterol is the most atherogenic lipoprotein. logic therapy may be indicated after assessment of ASCVD The AHA/ACC cholesterol management guideline, however, risk. recommends initiation of fixed-dose statin therapy in patients with ASCVD regardless of LDL cholesterol level, with subse- Therapeutic Lifestyle Changes quent lipid monitoring. The primary utility of LDL cholesterol All patients at increased cardiovascular risk should be coun- measurement is therefore to identify patients without known seled regarding therapeutic lifestyle changes, including dietary ASCVD who will benefit from treatment with statin therapy modification, regular physical activity, weight loss, and smok- and to assess response to therapy. ing cessation. In patients with elevated LDL cholesterol levels, secondary Patients should be encouraged to adhere to a diet that causes, including hypothyroidism, poorly controlled diabetes focuses on consumption of fruits, vegetables, fiber, and mono- mellitus, nephrotic syndrome, and medications (e.g., glucocor- unsaturated fats and minimizes intake of saturated and trans ticoids, diuretics, amiodarone), should be considered. In patients fats, simple carbohydrates, and red meats. Examples of heart- without a secondary cause, genetic testing for familial hypercho- healthy diets include the DASH (Dietary Approaches to Stop lesterolemia is appropriate in patients with an LDL cholesterol Hypertension) and Mediterranean diets. The AHA/ACC addi- level of 250 mg/dL or higher (=6.47 mmol/L) and in those tionally recommend reducing the percentage of calories from who have an LDL cholesterol level of 190 mg/dL or higher saturated fat (<7% of calories from saturated fat; <6% of calo- (24.92 mmol/L) as well as a first-degree relative with a similar ries from saturated fat in patients at high cardiovascular risk) LDL cholesterol elevation or premature coronary artery disease. and the percentage of calories from trans fats. Replacing satu- rated fats with polyunsaturated fats has been shown to reduce Triglycerides LDL cholesterol levels and cardiovascular mortality. To facili- Elevated triglyceride levels (>150 mg/dL [1.69 mmol/L]) are tate these changes, clinicians should provide patients with independently associated with increased ASCVD risk; however, educational resources and, when appropriate, refer them to a it is uncertain whether reducing triglyceride levels decreases dietitian. Behavioral support programs may increase adher- risk. Causes of hypertriglyceridemia include diabetes; excessive ence to appropriate diets, and referral should be considered. alcohol intake; hypothyroidism; and medications, such as glu- The AHA/ACC also recommends that patients, including cocorticoids, protease inhibitors, and estrogens. Lifestyle fac- those with chronic medical conditions, engage in moderate to tors, including obesity and concentrated sugar intake, are also vigorous physical activity for a minimum of 150 min/wk. implicated. Patients with triglyceride levels of 500 mg/dL or Adults should perform muscle-strengthening exercises two to higher (=5.65 mmol/L) without an identifiable cause should be three times per week as well. evaluated for familial hypertriglyceridemia. Acute pancreatitis can be induced by triglyceride levels greater than 500 to 1000 mg/dL (>5.6-11.3 mmol/L). e All patients at increased cardiovascular risk should be HVC Triglyceride levels should be measured in selected patients counseled regarding therapeutic lifestyle changes, with pancreatitis, especially in cases of pancreatitis without a including dietary modification, regular physical activity, clear cause (such as alcohol use or biliary disease). weight loss, and smoking cessation.

The association between high LDL cholesterol levels and increased risk for ASCVD is widely accepted. Historically, cho- Management of Dyslipidemias lesterol treatment targeted specific LDL cholesterol goals Treatment with therapeutic lifestyle changes and pharmaco- because LDL cholesterol is the most atherogenic lipoprotein. logic therapy may be indicated after assessment of ASCVD The AHA/ACC cholesterol management guideline, however, risk. recommends initiation of fixed-dose statin therapy in patients with ASCVD regardless of LDL cholesterol level, with subse- Therapeutic Lifestyle Changes quent lipid monitoring. The primary utility of LDL cholesterol All patients at increased cardiovascular risk should be coun- measurement is therefore to identify patients without known seled regarding therapeutic lifestyle changes, including dietary ASCVD who will benefit from treatment with statin therapy modification, regular physical activity, weight loss, and smok- and to assess response to therapy. ing cessation. In patients with elevated LDL cholesterol levels, secondary Patients should be encouraged to adhere to a diet that causes, including hypothyroidism, poorly controlled diabetes focuses on consumption of fruits, vegetables, fiber, and mono- mellitus, nephrotic syndrome, and medications (e.g., glucocor- unsaturated fats and minimizes intake of saturated and trans ticoids, diuretics, amiodarone), should be considered. In patients fats, simple carbohydrates, and red meats. Examples of heart- without a secondary cause, genetic testing for familial hypercho- healthy diets include the DASH (Dietary Approaches to Stop lesterolemia is appropriate in patients with an LDL cholesterol Hypertension) and Mediterranean diets. The AHA/ACC addi- level of 250 mg/dL or higher (=6.47 mmol/L) and in those tionally recommend reducing the percentage of calories from who have an LDL cholesterol level of 190 mg/dL or higher saturated fat (<7% of calories from saturated fat; <6% of calo- (24.92 mmol/L) as well as a first-degree relative with a similar ries from saturated fat in patients at high cardiovascular risk) LDL cholesterol elevation or premature coronary artery disease. and the percentage of calories from trans fats. Replacing satu- rated fats with polyunsaturated fats has been shown to reduce Triglycerides LDL cholesterol levels and cardiovascular mortality. To facili- Elevated triglyceride levels (>150 mg/dL [1.69 mmol/L]) are tate these changes, clinicians should provide patients with independently associated with increased ASCVD risk; however, educational resources and, when appropriate, refer them to a it is uncertain whether reducing triglyceride levels decreases dietitian. Behavioral support programs may increase adher- risk. Causes of hypertriglyceridemia include diabetes; excessive ence to appropriate diets, and referral should be considered. alcohol intake; hypothyroidism; and medications, such as glu- The AHA/ACC also recommends that patients, including cocorticoids, protease inhibitors, and estrogens. Lifestyle fac- those with chronic medical conditions, engage in moderate to tors, including obesity and concentrated sugar intake, are also vigorous physical activity for a minimum of 150 min/wk. implicated. Patients with triglyceride levels of 500 mg/dL or Adults should perform muscle-strengthening exercises two to higher (=5.65 mmol/L) without an identifiable cause should be three times per week as well. evaluated for familial hypertriglyceridemia. Acute pancreatitis can be induced by triglyceride levels greater than 500 to 1000 mg/dL (>5.6-11.3 mmol/L). e All patients at increased cardiovascular risk should be HVC Triglyceride levels should be measured in selected patients counseled regarding therapeutic lifestyle changes, with pancreatitis, especially in cases of pancreatitis without a including dietary modification, regular physical activity, clear cause (such as alcohol use or biliary disease). weight loss, and smoking cessation. HDL Cholesterol Pharmacologic Therapy HDL cholesterol is a protective factor against the development Statins are the mainstay of pharmacologic therapy for dyslipi- of ASCVD and is an important component in assessment of demia and the primary and secondary prevention of ASCVD. ASCVD risk. However, a causative link between low HDL Statin dosages for high- and moderate-intensity therapy are cholesterol levels and ASCVD has not been established. presented in Table 40.

HDL Cholesterol Pharmacologic Therapy HDL cholesterol is a protective factor against the development Statins are the mainstay of pharmacologic therapy for dyslipi- of ASCVD and is an important component in assessment of demia and the primary and secondary prevention of ASCVD. ASCVD risk. However, a causative link between low HDL Statin dosages for high- and moderate-intensity therapy are cholesterol levels and ASCVD has not been established. presented in Table 40. 67

Dyslipidemia TABLE 40. High- and Moderate-Intensity Statin Therapy high-intensity statin therapy should be initiated to reduce the LDL cholesterol level by 50% or more. The AHA/ACC choles- | Therapy Intensity Drug and Dosage | terol management guideline identifies two other major cate- | High intensity Atorvastatin, 40-80 mg/d gories of higher-risk patients that benefit from primary Rosuvastatin, 20-40 mg/d prevention statin therapy without calculating the 10-year Moderate intensity Atorvastatin, 10 mg/d ASCVD risk. Adults of any age with an LDL cholesterol level of Rosuvastatin, 10 mg/d 190 mg/dL or higher (=4.92 mmol/L) should be started on

TABLE 40. High- and Moderate-Intensity Statin Therapy high-intensity statin therapy should be initiated to reduce the LDL cholesterol level by 50% or more. The AHA/ACC choles- | Therapy Intensity Drug and Dosage | terol management guideline identifies two other major cate- | High intensity Atorvastatin, 40-80 mg/d gories of higher-risk patients that benefit from primary Rosuvastatin, 20-40 mg/d prevention statin therapy without calculating the 10-year Moderate intensity Atorvastatin, 10 mg/d ASCVD risk. Adults of any age with an LDL cholesterol level of Rosuvastatin, 10 mg/d 190 mg/dL or higher (=4.92 mmol/L) should be started on Simvastatin, 20-40 mg/d | high-intensity statin therapy, and adults aged 40 to 75 years with diabetes should be started on moderate-intensity statin Pravastatin, 40 mg/d therapy. In patients with diabetes and additional ASCVD risk Lovastatin, 40 mg/d factors, the 10-year ASCVD risk can be calculated to determine Fluvastatin, 40 mg twice daily whether high-intensity statin therapy is indicated. In adults at intermediate risk according to the Pooled Cohort Equations, the presence of risk-enhancing factors may Effective adjunctive LDL cholesterol-lowering drugs justify initiation of moderate-intensity statin therapy (Table 42). include ezetimibe, bile acid sequestrants, and proprotein con- When the decision about initiating statin therapy remains vertase subtilisin/kexin type 9 (PCSK9) inhibitors (Table 41). uncertain, it is reasonable to obtain a coronary artery calcium Fibrates and niacin are not recommended as adjuncts to statin (CAC) score to guide therapeutic decisions (see MKSAP 19 therapy to reduce LDL cholesterol levels. Cardiovascular Medicine). If the CAC score is 0, it is appropri- ate to withhold statin therapy and reassess in 5 to 10 years as Primary Prevention of Atherosclerotic long as higher-risk conditions (e.g., family history of prema- Cardiovascular Disease ture ASCVD, cigarette smoking) are absent. If the CAC score is The AHA/ACC recommendations for primary prevention of 1 to 99, it is reasonable to initiate statin therapy for most ASCVD are summarized in Figure 22. Regardless of risk cate- patients aged 55 years or older. In patients with a CAC score of gory, physicians should engage all patients in a discussion that 100 or higher or at the 75th percentile or higher, it is reasona- considers risk factors, healthy lifestyle, benefits and risks of ble to initiate statin therapy regardless of age. Patients at bor- drug therapy, and patient preferences. derline or low risk generally do not require statin therapy, but Adults aged 40 to 75 years without diabetes and with an therapy can be discussed with patients at borderline risk when LDL cholesterol level of 70 mg/dL to 189 mg/dL (1.81-4.90 additional risk-enhancing factors are present. mmol/L) should undergo risk assessment for the primary pre- Nonstatin drugs to lower LDL cholesterol should be con- vention of ASCVD using the Pooled Cohort Equations. The sidered alone or in combination with statins in patients who 10-year risk for ASCVD can be categorized as high (=20%), do not achieve adequate LDL cholesterol reduction with statin intermediate (=7.5% to <20%), borderline (5% to <7.5%), or low therapy or cannot tolerate statins, especially high-risk patients. (<5%). In adults aged 40 to 75 years at high risk for ASCVD, Before nonstatin drugs are initiated, patient preferences as

Simvastatin, 20-40 mg/d | high-intensity statin therapy, and adults aged 40 to 75 years with diabetes should be started on moderate-intensity statin Pravastatin, 40 mg/d therapy. In patients with diabetes and additional ASCVD risk Lovastatin, 40 mg/d factors, the 10-year ASCVD risk can be calculated to determine Fluvastatin, 40 mg twice daily whether high-intensity statin therapy is indicated. In adults at intermediate risk according to the Pooled Cohort Equations, the presence of risk-enhancing factors may Effective adjunctive LDL cholesterol-lowering drugs justify initiation of moderate-intensity statin therapy (Table 42). include ezetimibe, bile acid sequestrants, and proprotein con- When the decision about initiating statin therapy remains vertase subtilisin/kexin type 9 (PCSK9) inhibitors (Table 41). uncertain, it is reasonable to obtain a coronary artery calcium Fibrates and niacin are not recommended as adjuncts to statin (CAC) score to guide therapeutic decisions (see MKSAP 19 therapy to reduce LDL cholesterol levels. Cardiovascular Medicine). If the CAC score is 0, it is appropri- ate to withhold statin therapy and reassess in 5 to 10 years as Primary Prevention of Atherosclerotic long as higher-risk conditions (e.g., family history of prema- Cardiovascular Disease ture ASCVD, cigarette smoking) are absent. If the CAC score is The AHA/ACC recommendations for primary prevention of 1 to 99, it is reasonable to initiate statin therapy for most ASCVD are summarized in Figure 22. Regardless of risk cate- patients aged 55 years or older. In patients with a CAC score of gory, physicians should engage all patients in a discussion that 100 or higher or at the 75th percentile or higher, it is reasona- considers risk factors, healthy lifestyle, benefits and risks of ble to initiate statin therapy regardless of age. Patients at bor- drug therapy, and patient preferences. derline or low risk generally do not require statin therapy, but Adults aged 40 to 75 years without diabetes and with an therapy can be discussed with patients at borderline risk when LDL cholesterol level of 70 mg/dL to 189 mg/dL (1.81-4.90 additional risk-enhancing factors are present. mmol/L) should undergo risk assessment for the primary pre- Nonstatin drugs to lower LDL cholesterol should be con- vention of ASCVD using the Pooled Cohort Equations. The sidered alone or in combination with statins in patients who 10-year risk for ASCVD can be categorized as high (=20%), do not achieve adequate LDL cholesterol reduction with statin intermediate (=7.5% to <20%), borderline (5% to <7.5%), or low therapy or cannot tolerate statins, especially high-risk patients. (<5%). In adults aged 40 to 75 years at high risk for ASCVD, Before nonstatin drugs are initiated, patient preferences as TABLE 41. Characteristics of Lipid-Lowering Nonstatin Drugs

Simvastatin, 20-40 mg/d | high-intensity statin therapy, and adults aged 40 to 75 years with diabetes should be started on moderate-intensity statin Pravastatin, 40 mg/d therapy. In patients with diabetes and additional ASCVD risk Lovastatin, 40 mg/d factors, the 10-year ASCVD risk can be calculated to determine Fluvastatin, 40 mg twice daily whether high-intensity statin therapy is indicated. In adults at intermediate risk according to the Pooled Cohort Equations, the presence of risk-enhancing factors may Effective adjunctive LDL cholesterol-lowering drugs justify initiation of moderate-intensity statin therapy (Table 42). include ezetimibe, bile acid sequestrants, and proprotein con- When the decision about initiating statin therapy remains vertase subtilisin/kexin type 9 (PCSK9) inhibitors (Table 41). uncertain, it is reasonable to obtain a coronary artery calcium Fibrates and niacin are not recommended as adjuncts to statin (CAC) score to guide therapeutic decisions (see MKSAP 19 therapy to reduce LDL cholesterol levels. Cardiovascular Medicine). If the CAC score is 0, it is appropri- ate to withhold statin therapy and reassess in 5 to 10 years as Primary Prevention of Atherosclerotic long as higher-risk conditions (e.g., family history of prema- Cardiovascular Disease ture ASCVD, cigarette smoking) are absent. If the CAC score is The AHA/ACC recommendations for primary prevention of 1 to 99, it is reasonable to initiate statin therapy for most ASCVD are summarized in Figure 22. Regardless of risk cate- patients aged 55 years or older. In patients with a CAC score of gory, physicians should engage all patients in a discussion that 100 or higher or at the 75th percentile or higher, it is reasona- considers risk factors, healthy lifestyle, benefits and risks of ble to initiate statin therapy regardless of age. Patients at bor- drug therapy, and patient preferences. derline or low risk generally do not require statin therapy, but Adults aged 40 to 75 years without diabetes and with an therapy can be discussed with patients at borderline risk when LDL cholesterol level of 70 mg/dL to 189 mg/dL (1.81-4.90 additional risk-enhancing factors are present. mmol/L) should undergo risk assessment for the primary pre- Nonstatin drugs to lower LDL cholesterol should be con- vention of ASCVD using the Pooled Cohort Equations. The sidered alone or in combination with statins in patients who 10-year risk for ASCVD can be categorized as high (=20%), do not achieve adequate LDL cholesterol reduction with statin intermediate (=7.5% to <20%), borderline (5% to <7.5%), or low therapy or cannot tolerate statins, especially high-risk patients. (<5%). In adults aged 40 to 75 years at high risk for ASCVD, Before nonstatin drugs are initiated, patient preferences as TABLE 41. Characteristics of Lipid-Lowering Nonstatin Drugs | Medication LDL Cholesterol ASCVD Risk Adverse Effects Approximate | | Lowering Reduction Cost |

| Medication LDL Cholesterol ASCVD Risk Adverse Effects Approximate | | Lowering Reduction Cost | PCSK9 inhibitors WW Wt Nasopharyngitis, injection-site reactions, possible $$$ | cognitive effects | Ezetimibe WW dala, Diarrhea, arthralgia, abdominal pain, myositis, $$-$$$ elevated liver aminotransferase levels when | combined with statins Bile acid LW 4 (cholestyramine) Constipation, bloating, nausea, elevated liver $$ sequestrants aminotransferase levels, interference with drug absorption Increased triglyceride levels only if baseline levels | are elevated | Fibrates fb Not well Myositis (especially if combined with statins), nausea, $$ determined abdominal pain | Phytosterols L Not well Mild bloating; diarrhea or constipation $-$$ | determined Icosapent ethyl - iw Pneumonia, atrial fibrillation $$

| Phytosterols L Not well Mild bloating; diarrhea or constipation $-$$ | determined Icosapent ethyl - iw Pneumonia, atrial fibrillation $$ | ASCVD = atherosclerotic cardiovascular disease; PCSK9 = proprotein convertase subtilisin/kexin type 9. eae 68

Dyslipidemia Lipid profile i | LDL cholesterol 70-189 mg/dL LDL cholesterol =>190 mg/dL (1.81-4.90 mmol/L) (4.92 mmol/L)

i | LDL cholesterol 70-189 mg/dL LDL cholesterol =>190 mg/dL (1.81-4.90 mmol/L) (4.92 mmol/L) ——— Age 40-75 years Age >75 years | High-intensity statin therapy to achieve 250% reduction in LDL cholesterol | | and/or LDL cholesterol <100 mg/dL (<2.59 mmol/L) Ezetimibe may be added if Diabetes mellitus Balance benefits and risks necessary to achieve goal Moderate-intensity statin therapy may be reasonable

——— Age 40-75 years Age >75 years | High-intensity statin therapy to achieve 250% reduction in LDL cholesterol | | and/or LDL cholesterol <100 mg/dL (<2.59 mmol/L) Ezetimibe may be added if Diabetes mellitus Balance benefits and risks necessary to achieve goal Moderate-intensity statin therapy may be reasonable Yes i =

——— Age 40-75 years Age >75 years | High-intensity statin therapy to achieve 250% reduction in LDL cholesterol | | and/or LDL cholesterol <100 mg/dL (<2.59 mmol/L) Ezetimibe may be added if Diabetes mellitus Balance benefits and risks necessary to achieve goal Moderate-intensity statin therapy may be reasonable Yes i = Multiple additional Calculate 10-year ASCVD risk? risk factors’ or elevated ASCVD 10-year risk 1 + \ \ Yes | 1, | Risk =7.5% to <20% | Risk =20% Consider high-intensity statin therapy to achieve LDL cholesterol Moderate-intensity statin therapy to achieve LDL cholesterol f reduction 250% reduction of 30%-49% Moderate-intensity statin High-intensity statin therapy to achieve LDL therapy to achieve cholesterol reduction of LDL cholesterol 30%-49% if risk-enhancing reduction 250% factors“? favor treatment

Multiple additional Calculate 10-year ASCVD risk? risk factors’ or elevated ASCVD 10-year risk 1 + \ \ Yes | 1, | Risk =7.5% to <20% | Risk =20% Consider high-intensity statin therapy to achieve LDL cholesterol Moderate-intensity statin therapy to achieve LDL cholesterol f reduction 250% reduction of 30%-49% Moderate-intensity statin High-intensity statin therapy to achieve LDL therapy to achieve cholesterol reduction of LDL cholesterol 30%-49% if risk-enhancing reduction 250% factors“? favor treatment FIGURE 22. Recommendations for statin therapy in the primary prevention of ASCVD. ASCVD = atherosclerotic cardiovascular disease. *Additional risk factors include long duration (=10 years for type 2 diabetes mellitus or >20 years for type 1 diabetes mellitus), alb ia (30 mg of albumin/g creatinine), dgl lar filtration rate less than 60 mUmin/1.73 m?, retinopathy, neuropathy, and ankle-brachial index less than 0.9.

FIGURE 22. Recommendations for statin therapy in the primary prevention of ASCVD. ASCVD = atherosclerotic cardiovascular disease. *Additional risk factors include long duration (=10 years for type 2 diabetes mellitus or >20 years for type 1 diabetes mellitus), alb ia (30 mg of albumin/g creatinine), dgl lar filtration rate less than 60 mUmin/1.73 m?, retinopathy, neuropathy, and ankle-brachial index less than 0.9. Risk for fatal and nonfatal myocardial infarction or stroke. An ASCVD risk calculator is available at http://tools.acc.org/ASCVD-Risk-Estimator-Plus?#!/calculate/estimate/. ‘See Table 42 for a list of ASCVD risk-enhancing factors. 4If the decision about initiating statin therapy remains uncertain, it is reasonable to obtain a coronary artery calcium score to guide therapeutic decisions. Recommendations from Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol: a report of the American College of Cardiology/ American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2019;139:e1082-43. [PMID: 30586774] doi:10.1161/CIR.0000000000000625

Recommendations from Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol: a report of the American College of Cardiology/ American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2019;139:e1082-43. [PMID: 30586774] doi:10.1161/CIR.0000000000000625 well as anticipated ASCVD risk reduction and adverse effects The U.S. Department of Veterans Affairs and U.S. should be discussed. Ezetimibe can be used for primary pre- Department of Defense, in their 2020 joint clinical practice vention of ASCVD in patients with an initial LDL cholesterol guideline on managing dyslipidemia to reduce cardiovascular level of 190 mg/dL or higher (=4.92 mmol/L) who do not disease risk, recommend moderate-intensity statin therapy for achieve a 50% reduction in LDL cholesterol while taking maxi- primary prevention in patients with a 10-year cardiovascular mally tolerated statin therapy or who have an LDL cholesterol risk of 12% or higher, an LDL cholesterol level of 190 mg/dL or level of 100 mg/dL or higher (=2.59 mmol/L). higher (24.92 mmol/L), or diabetes. A summary of the guide- The USPSTF recommendations for primary prevention line recommendations is provided in Table 43. statin therapy differ from those of the AHA/ACC. In asympto- matic adults aged 40 to 75 years without ASCVD who have at Secondary Prevention of Atherosclerotic least one ASCVD risk factor (dyslipidemia, diabetes, hyperten- Cardiovascular Disease sion, or smoking), the USPSTF recommends low- to moderate- Patients eligible for secondary prevention therapy include intensity statin therapy in those with a calculated 10-year those with acute coronary syndrome (ACS); history of myocar- ASCVD event risk of 10% or higher (grade B recommendation) dial infarction (MI); stable or unstable angina; coronary or and selective consideration of low- to moderate-intensity sta- other arterial revascularization; stroke; transient ischemic tin therapy in those with a calculated 10-year ASCVD event attack; or peripheral artery disease, including aortic aneu- risk of 7.5% to 10% (grade C recommendation). rysm. According to AHA/ACC guidelines, high-intensity statin

well as anticipated ASCVD risk reduction and adverse effects The U.S. Department of Veterans Affairs and U.S. should be discussed. Ezetimibe can be used for primary pre- Department of Defense, in their 2020 joint clinical practice vention of ASCVD in patients with an initial LDL cholesterol guideline on managing dyslipidemia to reduce cardiovascular level of 190 mg/dL or higher (=4.92 mmol/L) who do not disease risk, recommend moderate-intensity statin therapy for achieve a 50% reduction in LDL cholesterol while taking maxi- primary prevention in patients with a 10-year cardiovascular mally tolerated statin therapy or who have an LDL cholesterol risk of 12% or higher, an LDL cholesterol level of 190 mg/dL or level of 100 mg/dL or higher (=2.59 mmol/L). higher (24.92 mmol/L), or diabetes. A summary of the guide- The USPSTF recommendations for primary prevention line recommendations is provided in Table 43. statin therapy differ from those of the AHA/ACC. In asympto- matic adults aged 40 to 75 years without ASCVD who have at Secondary Prevention of Atherosclerotic least one ASCVD risk factor (dyslipidemia, diabetes, hyperten- Cardiovascular Disease sion, or smoking), the USPSTF recommends low- to moderate- Patients eligible for secondary prevention therapy include intensity statin therapy in those with a calculated 10-year those with acute coronary syndrome (ACS); history of myocar- ASCVD event risk of 10% or higher (grade B recommendation) dial infarction (MI); stable or unstable angina; coronary or and selective consideration of low- to moderate-intensity sta- other arterial revascularization; stroke; transient ischemic tin therapy in those with a calculated 10-year ASCVD event attack; or peripheral artery disease, including aortic aneu- risk of 7.5% to 10% (grade C recommendation). rysm. According to AHA/ACC guidelines, high-intensity statin 69

Dyslipidemia The PCSK9 inhibitors are monoclonal antibodies that bind TABLE 42. Risk-Enhancing Factors for Clinician-Patient Risk Discussion to serine protease PCSK9, a liver enzyme that degrades hepato- cyte LDL receptors. Treatment with PCSK9 inhibitors produces Family history of premature ASCVD (males, age <55 y; females, age <65 y) an additional 43% to 64% reduction in LDL cholesterol when

The PCSK9 inhibitors are monoclonal antibodies that bind TABLE 42. Risk-Enhancing Factors for Clinician-Patient Risk Discussion to serine protease PCSK9, a liver enzyme that degrades hepato- cyte LDL receptors. Treatment with PCSK9 inhibitors produces Family history of premature ASCVD (males, age <55 y; females, age <65 y) an additional 43% to 64% reduction in LDL cholesterol when Primary hypercholesterolemia (LDL cholesterol 160-189 mg/dL added to statin therapy. Barriers to the use of PCSK9 inhibitors [4.14-4.90 mmol/L]; non-HDL cholesterol 190-219 mg/dL | include high cost and subcutaneous administration. Adding a [4.92-5.67 mmol/L])? PCSK9 inhibitor can be considered for secondary prevention in Metabolic syndrome (increased waist circumference, elevated very high-risk patients if the LDL cholesterol level remains triglycerides [>150 mg/dL {1.69 mmol/L}], elevated blood 70 mg/dL or higher (21.81 mmol/L) or the non-HDL cholesterol pressure, elevated glucose, and low HDL cholesterol [<40 mg/dL | {1.04 mmol/L} in men; <50 mg/dL {1.29 mmol/L} in women] are | level is 100 mg/dL or higher (2.59 mmol/L) despite maximally factors; tally of three makes the diagnosis) | tolerated lipid-lowering therapy, which includes a statin plus | Chronic kidney disease (eGFR 15-59 mL/min/1.73 m? with or ezetimibe. The long-term safety of PCSK9 inhibitors is without albuminuria; not treated with dialysis or kidney unknown, and cost-effectiveness is low. transplantation) For secondary prevention, the 2020 U.S. Department of Chronic inflammatory conditions, such as psoriasis, RA, or Veterans Affairs and U.S. Department of Defense cholesterol HIV/AIDS guideline recommends at least moderate-intensity statin ther- History of premature menopause (before age 40 y) and history apy and, in higher-risk patients, high-intensity statin therapy of pregnancy-associated conditions that increase later ASCVD risk, such as preeclampsia (see Table 43). Higher-risk patients include those with MI or ACS in the past 12 months; recurrent ACS, MI, or stroke; or High-risk race/ethnicities (e.g., South Asian ancestry) established cardiovascular disease with additional risk factors. Lipid/biomarkers: Associated with increased ASCVD risk

Primary hypercholesterolemia (LDL cholesterol 160-189 mg/dL added to statin therapy. Barriers to the use of PCSK9 inhibitors [4.14-4.90 mmol/L]; non-HDL cholesterol 190-219 mg/dL | include high cost and subcutaneous administration. Adding a [4.92-5.67 mmol/L])? PCSK9 inhibitor can be considered for secondary prevention in Metabolic syndrome (increased waist circumference, elevated very high-risk patients if the LDL cholesterol level remains triglycerides [>150 mg/dL {1.69 mmol/L}], elevated blood 70 mg/dL or higher (21.81 mmol/L) or the non-HDL cholesterol pressure, elevated glucose, and low HDL cholesterol [<40 mg/dL | {1.04 mmol/L} in men; <50 mg/dL {1.29 mmol/L} in women] are | level is 100 mg/dL or higher (2.59 mmol/L) despite maximally factors; tally of three makes the diagnosis) | tolerated lipid-lowering therapy, which includes a statin plus | Chronic kidney disease (eGFR 15-59 mL/min/1.73 m? with or ezetimibe. The long-term safety of PCSK9 inhibitors is without albuminuria; not treated with dialysis or kidney unknown, and cost-effectiveness is low. transplantation) For secondary prevention, the 2020 U.S. Department of Chronic inflammatory conditions, such as psoriasis, RA, or Veterans Affairs and U.S. Department of Defense cholesterol HIV/AIDS guideline recommends at least moderate-intensity statin ther- History of premature menopause (before age 40 y) and history apy and, in higher-risk patients, high-intensity statin therapy of pregnancy-associated conditions that increase later ASCVD risk, such as preeclampsia (see Table 43). Higher-risk patients include those with MI or ACS in the past 12 months; recurrent ACS, MI, or stroke; or High-risk race/ethnicities (e.g., South Asian ancestry) established cardiovascular disease with additional risk factors. Lipid/biomarkers: Associated with increased ASCVD risk Persistently? elevated, primary hypertriglyceridemia (2175 mg/dL | Statin Monitoring, Safety, and Intolerance [1.98 mmol/L]) A lipid panel should be obtained 4 to 12 weeks after initiation If measured: of lipid-lowering therapy to assess treatment adherence and 1. Elevated high-sensitivity C-reactive protein (22.0 mg/L) response. Patients who do not achieve adequate reduction in 2. Elevated Lp(a): A relative indication for its measurement is LDL cholesterol (50% reduction with high-intensity statin family history of premature ASCVD. An Lp(a) 250 mg/dL therapy, 30%-49% reduction with moderate-intensity statin (0.50 g/L) or 2125 nmol/L constitutes a risk-enhancing factor, especially at higher levels of Lp(a) therapy) should be assessed for medication adherence and intensify lifestyle modifications. Once treatment goals have | 3. Elevated apoB 130 mg/dL (1.3 g/L): A relative indication for its measurement would be triglycerides >200 mg/dL been achieved, lipid levels should be measured every 3 to (2.26 mmol/L). A level 2130 mg/dL (1.3 g/L) corresponds 12 months as indicated. to an LDL cholesterol >160 mg/dL (4.14 mmol/L) and Statins are generally safe and well tolerated. They can constitutes a risk-enhancing factor cause asymptomatic, dose-related elevations in aminotrans- 4. ABI <0.9 ferase levels in approximately 1% of patients, but liver injury ABI = ankle-brachial index; apoB = apolipoprotein B; ASCVD = atherosclerotic occurs in less than 0.001% of patients. Although observational cardiovascular disease; eGFR = estimated glomerular filtration rate; Lp(a) = lipoprotein(a); RA = rheumatoid arthritis. studies have suggested higher rates, data from randomized tri-

Persistently? elevated, primary hypertriglyceridemia (2175 mg/dL | Statin Monitoring, Safety, and Intolerance [1.98 mmol/L]) A lipid panel should be obtained 4 to 12 weeks after initiation If measured: of lipid-lowering therapy to assess treatment adherence and 1. Elevated high-sensitivity C-reactive protein (22.0 mg/L) response. Patients who do not achieve adequate reduction in 2. Elevated Lp(a): A relative indication for its measurement is LDL cholesterol (50% reduction with high-intensity statin family history of premature ASCVD. An Lp(a) 250 mg/dL therapy, 30%-49% reduction with moderate-intensity statin (0.50 g/L) or 2125 nmol/L constitutes a risk-enhancing factor, especially at higher levels of Lp(a) therapy) should be assessed for medication adherence and intensify lifestyle modifications. Once treatment goals have | 3. Elevated apoB 130 mg/dL (1.3 g/L): A relative indication for its measurement would be triglycerides >200 mg/dL been achieved, lipid levels should be measured every 3 to (2.26 mmol/L). A level 2130 mg/dL (1.3 g/L) corresponds 12 months as indicated. to an LDL cholesterol >160 mg/dL (4.14 mmol/L) and Statins are generally safe and well tolerated. They can constitutes a risk-enhancing factor cause asymptomatic, dose-related elevations in aminotrans- 4. ABI <0.9 ferase levels in approximately 1% of patients, but liver injury ABI = ankle-brachial index; apoB = apolipoprotein B; ASCVD = atherosclerotic occurs in less than 0.001% of patients. Although observational cardiovascular disease; eGFR = estimated glomerular filtration rate; Lp(a) = lipoprotein(a); RA = rheumatoid arthritis. studies have suggested higher rates, data from randomized tri- 2Optimally, three determinations. als show that the incidence of statin-associated muscle symp-

Persistently? elevated, primary hypertriglyceridemia (2175 mg/dL | Statin Monitoring, Safety, and Intolerance [1.98 mmol/L]) A lipid panel should be obtained 4 to 12 weeks after initiation If measured: of lipid-lowering therapy to assess treatment adherence and 1. Elevated high-sensitivity C-reactive protein (22.0 mg/L) response. Patients who do not achieve adequate reduction in 2. Elevated Lp(a): A relative indication for its measurement is LDL cholesterol (50% reduction with high-intensity statin family history of premature ASCVD. An Lp(a) 250 mg/dL therapy, 30%-49% reduction with moderate-intensity statin (0.50 g/L) or 2125 nmol/L constitutes a risk-enhancing factor, especially at higher levels of Lp(a) therapy) should be assessed for medication adherence and intensify lifestyle modifications. Once treatment goals have | 3. Elevated apoB 130 mg/dL (1.3 g/L): A relative indication for its measurement would be triglycerides >200 mg/dL been achieved, lipid levels should be measured every 3 to (2.26 mmol/L). A level 2130 mg/dL (1.3 g/L) corresponds 12 months as indicated. to an LDL cholesterol >160 mg/dL (4.14 mmol/L) and Statins are generally safe and well tolerated. They can constitutes a risk-enhancing factor cause asymptomatic, dose-related elevations in aminotrans- 4. ABI <0.9 ferase levels in approximately 1% of patients, but liver injury ABI = ankle-brachial index; apoB = apolipoprotein B; ASCVD = atherosclerotic occurs in less than 0.001% of patients. Although observational cardiovascular disease; eGFR = estimated glomerular filtration rate; Lp(a) = lipoprotein(a); RA = rheumatoid arthritis. studies have suggested higher rates, data from randomized tri- 2Optimally, three determinations. als show that the incidence of statin-associated muscle symp- Reproduced with permission from Grundy SM, Stone NJ, Bailey AL, et al. 2018 toms is no greater than 1%, and the incidence of myopathy and AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA rhabdomyolysis is less than 0.1%. Before statin therapy is guideline on the management of blood cholesterol: a report of the American | College of Cardiology/American Heart Association Task Force on Clinical Practice started, liver chemistry tests should be obtained at baseline; Guidelines. Circulation. 2019;139:e1082-143. [PMID: 30586774] doi:10.1161/ | CIR.0000000000000625. ©2018, American Heart Association, Inc. however, liver chemistry tests and muscle enzyme studies should not be obtained during therapy in the absence of symp- therapy should be initiated in patients aged 75 years or younger toms. Statin therapy also increases the risk for newly diagnosed with ASCVD to achieve a reduction in LDL cholesterol of 50% type 2 diabetes by approximately 0.2% per year, although the or greater. If high-intensity statin therapy is contraindicated or risk appears to be restricted to patients with other risk factors not tolerated, moderate-intensity statin therapy should be ini- for diabetes. In patients with prior cerebrovascular disease, tiated to achieve a reduction in LDL cholesterol of 30% to 49%. statins may increase the risk for hemorrhagic stroke, but these Patients with a history of multiple major ASCVD events or drugs also reduce total stroke risk in this population. one major ASCVD event and multiple high-risk conditions are Most statin-related adverse effects can be reversed by stop- considered to be at very high risk. These patients may benefit ping treatment. In patients with statin intolerance, switching to from the addition of nonstatin drug therapy to maximally another statin is reasonable. Other options include decreasing tolerated statin therapy when the LDL cholesterol level remains the dosage and/or dosing frequency and, less preferably, dis- 70 mg/dL or higher (21.81 mmol/L). Ezetimibe is the preferred continuing statin therapy and initiating nonstatin drugs. nonstatin option when further lowering of LDL cholesterol is Statins have the potential to cause drug-drug interactions necessary. that predominantly increase the plasma concentrations of

Reproduced with permission from Grundy SM, Stone NJ, Bailey AL, et al. 2018 toms is no greater than 1%, and the incidence of myopathy and AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA rhabdomyolysis is less than 0.1%. Before statin therapy is guideline on the management of blood cholesterol: a report of the American | College of Cardiology/American Heart Association Task Force on Clinical Practice started, liver chemistry tests should be obtained at baseline; Guidelines. Circulation. 2019;139:e1082-143. [PMID: 30586774] doi:10.1161/ | CIR.0000000000000625. ©2018, American Heart Association, Inc. however, liver chemistry tests and muscle enzyme studies should not be obtained during therapy in the absence of symp- therapy should be initiated in patients aged 75 years or younger toms. Statin therapy also increases the risk for newly diagnosed with ASCVD to achieve a reduction in LDL cholesterol of 50% type 2 diabetes by approximately 0.2% per year, although the or greater. If high-intensity statin therapy is contraindicated or risk appears to be restricted to patients with other risk factors not tolerated, moderate-intensity statin therapy should be ini- for diabetes. In patients with prior cerebrovascular disease, tiated to achieve a reduction in LDL cholesterol of 30% to 49%. statins may increase the risk for hemorrhagic stroke, but these Patients with a history of multiple major ASCVD events or drugs also reduce total stroke risk in this population. one major ASCVD event and multiple high-risk conditions are Most statin-related adverse effects can be reversed by stop- considered to be at very high risk. These patients may benefit ping treatment. In patients with statin intolerance, switching to from the addition of nonstatin drug therapy to maximally another statin is reasonable. Other options include decreasing tolerated statin therapy when the LDL cholesterol level remains the dosage and/or dosing frequency and, less preferably, dis- 70 mg/dL or higher (21.81 mmol/L). Ezetimibe is the preferred continuing statin therapy and initiating nonstatin drugs. nonstatin option when further lowering of LDL cholesterol is Statins have the potential to cause drug-drug interactions necessary. that predominantly increase the plasma concentrations of 70

Dyslipidemia TABLE 43. Summary of the U.S. Department of Veterans Affairs/U.S. Department of Defense Dyslipidemia Pharmacotherapy Recommendations Recommendation Topic Conclusion oe Primary Prevention a Moderate-intensity statin therapy for patients with a 10-year CVD risk 212%, an LDL cholesterol level Recommended 2190 mg/dL (4.92 mmol/L), or diabetes mellitus Moderate-intensity statin therapy for patients with a 10-year CVD risk between 6% and 12% Suggested e e: PCSK@ inhibitors Recommended against Ezetimibe No recommendation Secondary Prevention a >? At least moderate-intensity statin therapy Recommended High-intensity statin therapy for higher-risk patients®> Suggested Adding ezetimibe to statin therapy for higher-risk patients?» Suggested PCSK@ inhibitor for higher-risk patients®° Suggested eee)

PCSK@ inhibitor for higher-risk patients®° Suggested eee) Other Medications, Supplements, and Nutraceuticals ee Adding icosapent ethyl to statin therapy for secondary prevention in patients with persistently elevated Suggested fasting triglyceride levels >150 mg/dL (1.69 mmol/L) Niacin for primary or secondary prevention Recommended against ee Adding fibrates to statin therapy for primary or secondary prevention Suggested against Omega-3 fatty acids as dietary supplements for primary or secondary prevention Suggested against oe ——.—_ _ {—- $]}]- Adding icosapent ethyl to statin therapy for primary prevention in patients with persistently elevated No recommendation fasting triglyceride levels >150 mg/dL (1.69 mmol/L) Monitoring Routine monitoring of lipid levels in patients receiving statin therapy Suggested against CVD = cardiovascular disease; PCSK9 = proprotein convertase subtilisin/kexin type 9. @In patients who are willing to intensify treatment after discussing the risk of high-intensity statin therapy.

Routine monitoring of lipid levels in patients receiving statin therapy Suggested against CVD = cardiovascular disease; PCSK9 = proprotein convertase subtilisin/kexin type 9. @In patients who are willing to intensify treatment after discussing the risk of high-intensity statin therapy. ’Higher-risk patients include those with a myocardial infarction or acute coronary syndrome in the past 12 months; recurrent acute coronary syndrome, myocardial infarction, or stroke; or established CVD with additional risk factors (e.g., currently smoking, diabetes, peripheral artery disease, or coronary revascularization). ‘In patients who are willing to intensify treatment after discussing the uncertain long-term safety and benefits. Information from O'Malley PG, Arnold MJ, Kelley C, et al. Management of dyslipidemia for cardiovascular disease risk reduction: synopsis of the 2020 updated U.S. Department of Veterans Affairs and U.S. Department of Defense clinical practice guideline. Ann Intern Med. 2020;173:822-9. [PMID: 32956597] doi:10.7326/M20-4648 statins, thereby increasing the risk for myopathy and rhabdo- myolysis. There are some interactions with common nonstatin ¢ The American Heart Association and American College cardiac medications (e.g., fibrates, dabigatran), and statins can of Cardiology recommend secondary prevention of ath- ——/ Warten, poner = ae ioe eee ie erosclerotic cardiovascular disease with high-intensity values. statins are contraindicated in pregnancy. statin therapy.

statins, thereby increasing the risk for myopathy and rhabdo- myolysis. There are some interactions with common nonstatin ¢ The American Heart Association and American College cardiac medications (e.g., fibrates, dabigatran), and statins can of Cardiology recommend secondary prevention of ath- ——/ Warten, poner = ae ioe eee ie erosclerotic cardiovascular disease with high-intensity values. statins are contraindicated in pregnancy. statin therapy. RENROINTS. CORRS eee kata eee e A lipid panel should be obtained 4 to 12 weeks after sta- e For primary prevention of atherosclerotic cardiovascu- tin therapy initiation to determine treatment adherence lar disease (ASCVD), the American Heart Association and response to therapy. and American College of Cardiology recommend e In patients treated with statin therapy, liver chemistry HVC (1) high-intensity statin therapy for patients with tests and muscle enzyme studies should not be rou- 10-year ASCVD risk of 20% or higher, (2) high-intensity tinely obtained in the absence of symptoms of liver statin therapy for an LDL cholesterol level of 190 mg/dL dysfunction or myopathy. or higher (24.92 mmol/L), (3) moderate-intensity statin therapy in patients aged 40 to 75 years with diabetes Management of Hypertriglyceridemia mellitus, and (4) moderate-intensity statin therapy for patients aged 40 to 75 years with risk-enhancing factors Therapeutic lifestyle changes are the cornerstone of manage-

RENROINTS. CORRS eee kata eee e A lipid panel should be obtained 4 to 12 weeks after sta- e For primary prevention of atherosclerotic cardiovascu- tin therapy initiation to determine treatment adherence lar disease (ASCVD), the American Heart Association and response to therapy. and American College of Cardiology recommend e In patients treated with statin therapy, liver chemistry HVC (1) high-intensity statin therapy for patients with tests and muscle enzyme studies should not be rou- 10-year ASCVD risk of 20% or higher, (2) high-intensity tinely obtained in the absence of symptoms of liver statin therapy for an LDL cholesterol level of 190 mg/dL dysfunction or myopathy. or higher (24.92 mmol/L), (3) moderate-intensity statin therapy in patients aged 40 to 75 years with diabetes Management of Hypertriglyceridemia mellitus, and (4) moderate-intensity statin therapy for patients aged 40 to 75 years with risk-enhancing factors Therapeutic lifestyle changes are the cornerstone of manage- and 10-year ASCVD risk of 7.5% to less than 20%. ment of elevated triglyceride levels. Medications that increase : triglyceride levels, such as estrogens, B-blockers, and gluco- (Continued) corticoids, should be avoided if possible. Omega-3 fatty acids, 71

Dyslipidemia which are found in many types of fish, reduce triglyceride consider premature menopause and history of pregnancy- levels and should be incorporated into the diet; however, associated disorders (hypertension, preeclampsia, gestational omega-3 fatty acid supplements do not reduce heart disease, diabetes), which increase ASCVD risk. The available evidence stroke, or death. does not indicate that statins are hazardous during pregnancy, In most patients, the value of pharmacologic treatment of but they have not been proved safe and are currently contrain- hypertriglyceridemia for preventing cardiovascular events has dicated in pregnant women. Women of childbearing age not been established. In adults with a 10-year ASCVD risk of should be counseled to use reliable contraception while taking 7.5% or higher anda triglyceride level of 175 mg/dL or higher a statin and to discontinue statin therapy 1 to 2 months before (21.98 mmol/L), initiating or intensifying statin therapy can be pregnancy is attempted. considered for a persistently elevated triglyceride level despite lifestyle interventions and addressing reversible factors. In patients with persistently elevated triglyceride levels despite Xanthomas statin therapy and either established cardiovascular disease or Xanthomas are lipid deposits in the connective tissue of the diabetes and multiple other risk factors, the addition of icosa- skin, tendons, or fasciae that manifest as yellow, orange, red- pent ethyl, a highly purified fish oil, may decrease the risk for dish, or yellow-brown papules, plaques, or nodules. They are cardiovascular events, an effect lacking for other omega-3 fatty associated with primary and secondary hyperlipidemias, and acids. Fibrates are the most effective pharmacotherapy for the type of xanthoma closely correlates with the type of lipopro- hypertriglyceridemia, resulting in a 30% to 50% reduction in tein that is elevated. The most common xanthoma types include triglyceride level; these agents are indicated in patients with eruptive, plane, xanthelasma, tuberous, and tendinous. severe hypertriglyceridemia to prevent acute pancreatitis. Eruptive xanthomas present as clusters of small erythe- Pharmacologic doses (4 g/d) of omega-3 fatty acid prepara- matous papules, typically on the extensor surfaces of the arms, tions are also effective at decreasing triglyceride levels. legs, and buttocks. Diagnosis is made by skin biopsy that shows lipid-laden macrophages in the dermis. Eruptive xan- thomas are pathognomonic of hypertriglyceridemia, with a e Therapeutic lifestyle changes are the cornerstone of vast number of patients also having a diagnosis of diabetes. management of hypertriglyceridemia. Lesions typically resolve with control of carbohydrate and lipid e Statin therapy can be considered in patients with a metabolism. Plane xanthomas are yellow-to-red plaques 10-year risk for atherosclerotic cardiovascular disease of found in the skin folds of the neck and trunk. They can be 7.5% or higher and a persistently elevated triglyceride associated with familial dyslipidemias and various hemato- level (2175 mg/dL [1.98 mmol/L]) despite lifestyle inter- logic cancers. Xanthelasma is a type of plane xanthoma local- ventions and addressing reversible factors. ized to the periorbital area, most commonly on the upper medial eyelid (Figure 23), and is characterized by soft, non- tender, nonpruritic plaques. Xanthelasma can occur without Management of Dyslipidemia in hyperlipidemia, particularly in older persons, but is often Special Populations associated with familial dyslipidemias when present in a Patients older than 75 years without known ASCVD and an LDL younger person. These lesions are a classic feature of primary cholesterol level of 70 mg/dL to 189 mg/dL (1.81-4.90 mmol/L) biliary cholangitis, a condition often associated with marked can be engaged in a discussion of the potential benefits of statin hypercholesterolemia. Tendon xanthomas are subcutaneous therapy for primary prevention. If statin therapy is selected, a moderate-intensity statin is recommended, but the benefit in this population is less robust than in other higher-risk groups. If the decision to initiate statin therapy is uncertain, measuring the CAC score can be helpful. Statin therapy can be avoided if the CAC score is 0. It is reasonable to forgo initiating a statin or to stop statin therapy in the face of functional decline, multiple comorbid conditions, frailty, or reduced life expectancy. For secondary prevention of ASCVD in patients older than 75 years, it is reasonable to continue statins in those who are already tolerating therapy; moderate-intensity therapy is benefi- cial and is preferable to high-intensity therapy in these patients. Initiation of statin therapy is not recommended in adults on dialysis for end-stage kidney disease, but it may be reason- able to continue a statin in patients already receiving therapy. FIGURE 23. Xanthelasma. This type of plane xanthoma presents as When discussing the benefits of statin therapy and life- asymptomatic, flat, yellow-to-orange papules or plaques around the eyelids and style modification with women, clinicians should specifically can be associated with familial dyslipidemia in young adults.

which are found in many types of fish, reduce triglyceride consider premature menopause and history of pregnancy- levels and should be incorporated into the diet; however, associated disorders (hypertension, preeclampsia, gestational omega-3 fatty acid supplements do not reduce heart disease, diabetes), which increase ASCVD risk. The available evidence stroke, or death. does not indicate that statins are hazardous during pregnancy, In most patients, the value of pharmacologic treatment of but they have not been proved safe and are currently contrain- hypertriglyceridemia for preventing cardiovascular events has dicated in pregnant women. Women of childbearing age not been established. In adults with a 10-year ASCVD risk of should be counseled to use reliable contraception while taking 7.5% or higher anda triglyceride level of 175 mg/dL or higher a statin and to discontinue statin therapy 1 to 2 months before (21.98 mmol/L), initiating or intensifying statin therapy can be pregnancy is attempted. considered for a persistently elevated triglyceride level despite lifestyle interventions and addressing reversible factors. In patients with persistently elevated triglyceride levels despite Xanthomas statin therapy and either established cardiovascular disease or Xanthomas are lipid deposits in the connective tissue of the diabetes and multiple other risk factors, the addition of icosa- skin, tendons, or fasciae that manifest as yellow, orange, red- pent ethyl, a highly purified fish oil, may decrease the risk for dish, or yellow-brown papules, plaques, or nodules. They are cardiovascular events, an effect lacking for other omega-3 fatty associated with primary and secondary hyperlipidemias, and acids. Fibrates are the most effective pharmacotherapy for the type of xanthoma closely correlates with the type of lipopro- hypertriglyceridemia, resulting in a 30% to 50% reduction in tein that is elevated. The most common xanthoma types include triglyceride level; these agents are indicated in patients with eruptive, plane, xanthelasma, tuberous, and tendinous. severe hypertriglyceridemia to prevent acute pancreatitis. Eruptive xanthomas present as clusters of small erythe- Pharmacologic doses (4 g/d) of omega-3 fatty acid prepara- matous papules, typically on the extensor surfaces of the arms, tions are also effective at decreasing triglyceride levels. legs, and buttocks. Diagnosis is made by skin biopsy that shows lipid-laden macrophages in the dermis. Eruptive xan- thomas are pathognomonic of hypertriglyceridemia, with a e Therapeutic lifestyle changes are the cornerstone of vast number of patients also having a diagnosis of diabetes. management of hypertriglyceridemia. Lesions typically resolve with control of carbohydrate and lipid e Statin therapy can be considered in patients with a metabolism. Plane xanthomas are yellow-to-red plaques 10-year risk for atherosclerotic cardiovascular disease of found in the skin folds of the neck and trunk. They can be 7.5% or higher and a persistently elevated triglyceride associated with familial dyslipidemias and various hemato- level (2175 mg/dL [1.98 mmol/L]) despite lifestyle inter- logic cancers. Xanthelasma is a type of plane xanthoma local- ventions and addressing reversible factors. ized to the periorbital area, most commonly on the upper medial eyelid (Figure 23), and is characterized by soft, non- tender, nonpruritic plaques. Xanthelasma can occur without Management of Dyslipidemia in hyperlipidemia, particularly in older persons, but is often Special Populations associated with familial dyslipidemias when present in a Patients older than 75 years without known ASCVD and an LDL younger person. These lesions are a classic feature of primary cholesterol level of 70 mg/dL to 189 mg/dL (1.81-4.90 mmol/L) biliary cholangitis, a condition often associated with marked can be engaged in a discussion of the potential benefits of statin hypercholesterolemia. Tendon xanthomas are subcutaneous therapy for primary prevention. If statin therapy is selected, a moderate-intensity statin is recommended, but the benefit in this population is less robust than in other higher-risk groups. If the decision to initiate statin therapy is uncertain, measuring the CAC score can be helpful. Statin therapy can be avoided if the CAC score is 0. It is reasonable to forgo initiating a statin or to stop statin therapy in the face of functional decline, multiple comorbid conditions, frailty, or reduced life expectancy. For secondary prevention of ASCVD in patients older than 75 years, it is reasonable to continue statins in those who are already tolerating therapy; moderate-intensity therapy is benefi- cial and is preferable to high-intensity therapy in these patients. Initiation of statin therapy is not recommended in adults on dialysis for end-stage kidney disease, but it may be reason- able to continue a statin in patients already receiving therapy. FIGURE 23. Xanthelasma. This type of plane xanthoma presents as When discussing the benefits of statin therapy and life- asymptomatic, flat, yellow-to-orange papules or plaques around the eyelids and style modification with women, clinicians should specifically can be associated with familial dyslipidemia in young adults. 72

Mental and Behavioral Health nodules occurring on the extensor tendons, especially on Although there are several definitions for metabolic syn- the hands and the Achilles tendon; they are associated with drome, the diagnostic criteria proposed by the National familial hypercholesterolemia. Cholesterol Education Program Adult Treatment Panel III hei minor modifications by the AHA/National Heart, Lung, and Blood Institute) are the most widely used (Table 44). The Metabolic Syndrome presence of a pathophysiologic link between the components Epidemiology and Pathophysiology of the metabolic syndrome is controversial; however, insulin Metabolic syndrome, also referred to as insulin resistance syn- resistance and adipocyte cytokines associated with metabolic drome, comprises a constellation of risk factors for cardiovas- syndrome appear to play a central role in inducing inflamma- cular disease and type 2 diabetes. It is a common condition, tory changes that contribute to ASCVD. occurring in 20% to 35% of U.S. adults. Management TABLE 44. Diagnostic Criteria for Metabolic Syndrome Treatment of metabolic syndrome focuses on addressing _ Measure (Any Three of Categorical Cut Points each of the component risk factors. Lifestyle modifications, | Five Constitute Diagnosis particularly weight loss and exercise, are the most important of Metabolic Syndrome) | treatment interventions. Routine pharmacotherapy is not

| Five Constitute Diagnosis particularly weight loss and exercise, are the most important of Metabolic Syndrome) | treatment interventions. Routine pharmacotherapy is not Elevated waist 2102 cm [40 in] in men; 288 cm recommended in patients who do not meet treatment criteria circumference?” [35 in] inwomen for the individual risk factors. In some studies, metformin | Elevated triglycerides >150 mg/dL(1.7 mmol/L) | has been shown to prevent progression to diabetes; however, or | it is inferior to lifestyle modifications, and its role in treating metabolic syndrome has not been established. On drug treatment for elevated | triglycerides | Reduced HDL cholesterol <40 mg/dL (1.03 mmol/L) in | men; <50 mg/dL (1.30 mmol/L) | in women Mental and Behavioral Health or

or | it is inferior to lifestyle modifications, and its role in treating metabolic syndrome has not been established. On drug treatment for elevated | triglycerides | Reduced HDL cholesterol <40 mg/dL (1.03 mmol/L) in | men; <50 mg/dL (1.30 mmol/L) | in women Mental and Behavioral Health or | On drug treatment for reduced | HDL cholesterol* Mood Disorders | Elevated blood pressure 2130 mm Hg systolic blood pressure Mood disorders are characterized by elevated or depressed | mood associated with psychomotor, cognitive, and/or vegeta- or | tive symptoms that cause significant functional impairment. | 285 mm Hg diastolic blood pressure | The two main groups of mood disorders are depressive disor- ders and bipolar disorder. or

| tive symptoms that cause significant functional impairment. | 285 mm Hg diastolic blood pressure | The two main groups of mood disorders are depressive disor- ders and bipolar disorder. or On antihypertensive drug | Depressive Disorders | treatment in a patient with a history of hypertension | The lifetime prevalence of depressive disorders in developed Elevated fasting glucose 2100 mg/dL (5.6 mmol/L) countries is approximately 20%. Women are affected almost or twice as often as are men. Peak onset is in the fifth decade of

Elevated fasting glucose 2100 mg/dL (5.6 mmol/L) countries is approximately 20%. Women are affected almost or twice as often as are men. Peak onset is in the fifth decade of On drug treatment for elevated | life, and incidence decreases in the elderly population. Depression is the leading cause of disability in the United glucose | States among individuals aged 15 to 44 years and is a major risk °To measure waist circumference, locate top of right iliac crest. Place a measuring | tape in a horizontal plane around abdomen at level of iliac crest. Before reading | factor for suicide. tape measure, ensure that tape is snug but does not compress the skin and is parallel to floor. Measurement is made at the end of a normal expiration. | Depressive disorders often initially present in the pri- mary care setting but are underdiagnosed because screening Some U.S. adults of non-Asian origin (e.g., White, Black, Hispanic) with marginally increased waist circumference (e.g., 94-101 cm [37-39 inches] in men and 80-87 cm is underperformed. Depressive symptoms are frequently [31-34 inches] in women) may have strong genetic contribution to insulin resistance and should benefit from changes in lifestyle habits, similar to men with categorical encountered in patients with chronic medical disease, either increases in waist circumference. Lower waist circumference cut point (e.g., 290 cm [35 inches] in men and 280 cm [31 inches] in women) appears to be appropriate as a direct result of the illness or as a response to illness- for Asian Americans. related disability. Depression commonly accompanies thy- ‘Fibrates and nicotinic acid are the most commonly used drugs for elevated roid disease, cancer, neurologic diseases (Parkinson disease), triglycerides and reduced HDL cholesterol. Patients taking one of these drugs are | presumed to have high triglycerides and low HDL cholesterol. heart failure, HIV infection, inflammatory bowel disease, and

On drug treatment for elevated | life, and incidence decreases in the elderly population. Depression is the leading cause of disability in the United glucose | States among individuals aged 15 to 44 years and is a major risk °To measure waist circumference, locate top of right iliac crest. Place a measuring | tape in a horizontal plane around abdomen at level of iliac crest. Before reading | factor for suicide. tape measure, ensure that tape is snug but does not compress the skin and is parallel to floor. Measurement is made at the end of a normal expiration. | Depressive disorders often initially present in the pri- mary care setting but are underdiagnosed because screening Some U.S. adults of non-Asian origin (e.g., White, Black, Hispanic) with marginally increased waist circumference (e.g., 94-101 cm [37-39 inches] in men and 80-87 cm is underperformed. Depressive symptoms are frequently [31-34 inches] in women) may have strong genetic contribution to insulin resistance and should benefit from changes in lifestyle habits, similar to men with categorical encountered in patients with chronic medical disease, either increases in waist circumference. Lower waist circumference cut point (e.g., 290 cm [35 inches] in men and 280 cm [31 inches] in women) appears to be appropriate as a direct result of the illness or as a response to illness- for Asian Americans. related disability. Depression commonly accompanies thy- ‘Fibrates and nicotinic acid are the most commonly used drugs for elevated roid disease, cancer, neurologic diseases (Parkinson disease), triglycerides and reduced HDL cholesterol. Patients taking one of these drugs are | presumed to have high triglycerides and low HDL cholesterol. heart failure, HIV infection, inflammatory bowel disease, and Reproduced with permission from Grundy SM, Cleeman JI, Daniels SR, et al; | diabetes mellitus. Medications, including glucocorticoids American Heart Association. Diagnosis and management of the metabolic '

On drug treatment for elevated | life, and incidence decreases in the elderly population. Depression is the leading cause of disability in the United glucose | States among individuals aged 15 to 44 years and is a major risk °To measure waist circumference, locate top of right iliac crest. Place a measuring | tape in a horizontal plane around abdomen at level of iliac crest. Before reading | factor for suicide. tape measure, ensure that tape is snug but does not compress the skin and is parallel to floor. Measurement is made at the end of a normal expiration. | Depressive disorders often initially present in the pri- mary care setting but are underdiagnosed because screening Some U.S. adults of non-Asian origin (e.g., White, Black, Hispanic) with marginally increased waist circumference (e.g., 94-101 cm [37-39 inches] in men and 80-87 cm is underperformed. Depressive symptoms are frequently [31-34 inches] in women) may have strong genetic contribution to insulin resistance and should benefit from changes in lifestyle habits, similar to men with categorical encountered in patients with chronic medical disease, either increases in waist circumference. Lower waist circumference cut point (e.g., 290 cm [35 inches] in men and 280 cm [31 inches] in women) appears to be appropriate as a direct result of the illness or as a response to illness- for Asian Americans. related disability. Depression commonly accompanies thy- ‘Fibrates and nicotinic acid are the most commonly used drugs for elevated roid disease, cancer, neurologic diseases (Parkinson disease), triglycerides and reduced HDL cholesterol. Patients taking one of these drugs are | presumed to have high triglycerides and low HDL cholesterol. heart failure, HIV infection, inflammatory bowel disease, and Reproduced with permission from Grundy SM, Cleeman JI, Daniels SR, et al; | diabetes mellitus. Medications, including glucocorticoids American Heart Association. Diagnosis and management of the metabolic ' and interferon, may also trigger depressive symptoms. syndrome: an American Heart Association/National Heart, Lung, and Blood Institute scientific statement. Circulation. 2005;112:2735-52. [PMID: 16157765] During evaluation for depression, clinicians must assess for doi:10.1161/CIRCULATIONAHA.105.169404. © 2005, Wolters Kluwer Health. these secondary causes.

and interferon, may also trigger depressive symptoms. syndrome: an American Heart Association/National Heart, Lung, and Blood Institute scientific statement. Circulation. 2005;112:2735-52. [PMID: 16157765] During evaluation for depression, clinicians must assess for doi:10.1161/CIRCULATIONAHA.105.169404. © 2005, Wolters Kluwer Health. these secondary causes. 73