-
Use high-intensity/max-tolerated statin to ↓ LDL-C by 50% for secondary prevention in ASCVD1 pts, per ACC/AHA.1 AACE/ACE specifies target LDL-C for pts at extreme and very high risk,2 and ADA concurs w/ statins for secondary prevention.3 Heart-healthy lifestyle1-3 - If very high-risk1 ASCVD: High-intensity/max-tolerated statin. If LDL-C ≥70 on max-tolerated statin, add-on ezetimibe reasonable. If LDL-C ≥70 (or non-HDL-C ≥100) despite max-tolerated statin + ezetimibe, reasonable to discuss add-on PCSK9i,1 per ACC/AHA; in pts w/ DM, target LDL-C reduction of ≥50% from baseline and LDL-C goal of <55, discuss add-on ezetimibe or PCSK9i (clinical CV benefit from adding ezetimibe or PCSK9i if target not achieved w/ max-tolerated statin),3 per ADA; AACE recommends LDL-C <55 for extreme risk, <70 for very high risk,2 and special considerations in women2 and pts w/ mixed dyslipidemia2
- If not very high-risk1 ASCVD: High-intensity statin; if not tolerated, then mod-intensity. If LDL-C ≥70 on max-tolerated statin, add-on ezetimibe may be reasonable, per ACC/AHA
- If HFrEF from ischemic heart dz w/ reasonable life expectancy (eg, 3-5y) and not on statin: Consider mod-intensity statin, per ACC/AHA1
Footnotes 1 2018 AHA/ACC/etc. Grundy SM, 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. J Am Coll Cardiol. 2019 June 25;73(24):3210-3227. Accessed 2/2/21
ASCVD = ACS, MI hx, angina, coronary/other arterial revasc, stroke, TIA, atherosclerotic PAD (including aortic aneurysm).
Lifestyle. Wt loss prn. Exercise: Average of 40min mod-intense aerobic activity 3-4x/wk. Tobacco cessation. Diet: ↑vegetables, fruits, nuts, whole grains, legumes, lean veg/animal protein, fish. ↓trans fats, red/processed meat, refined carbs, sugar beverages.
Very high-risk ASCVD pt = Hx multiple major ASCVD events OR 1 major event + multiple high-risk conditions:
Major ASCVD events
• ACS in past 12mo
• Hx of MI
• Ischemic stroke hx
• Symptomatic PAD (claudication hx w/ ABI <0.85 or previous revasc/amputation)
High-risk conditions
• ≥65 yo
• Heterozygous FH
• CABG or PCI outside of major ASCVD event
• DM
• HTN
• CHF
• CKD (eGFR 15-59 mL/min/1.73m 2)
• Current smoker
• LDL-C persistently ≥100 despite max-tolerated statin + ezetimibe
Risk enhancers
• FHx of premature ASCVD
• Personal hx: CKD, preeclampsia, menopause <40 yo, metabolic syndrome (3 of these: ↑waist circ., TG >150 mg/dL, ↑BP, ↑glucose, HDL <40 men or <50 women), inflammatory dz (RA, psoriasis, chronic HIV), high-risk ethnicity (eg, South Asian)
• Labs. LDL-C persistently ≥160, TG persistently ≥175. If measured:
hs-CRP ≥2 mg/dL, Lp(a) ≥50 mg/dL, apoB ≥130 mg/dL
• ABI <0.9 (if measured)
Diabetes-specific risk enhancers: long-standing DM (≥10y T2, ≥20y T1), albuminuria (≥30 mcg albumin/mg Cr), eGFR <60 mL/min/1.73m 2, retinopathy, neuropathy, ABI <0.9.
PCSK9i = evolocumab or alirocumab. Discuss net benefit, long-term (>3y) safety uncertainty, cost. Economic value of PCSK9i at mid-2018 list price: low value for ASCVD, uncertain for 1° prevention in severe hypercholesterolemia, incl FH pts w/o clinical ASCVD on max-tolerated statin + ezetimibe.
2 2020 AACE/ACE. Handelsman Y, et al. Consensus Statement by the American Association of Clinical Endocrinologists and American College of Endocrinology on the Management of Dyslipidemia and Prevention of Cardiovascular Disease Algorithm – 2020 Executive Summary. Endocr Pract. 2020. Oct:26(10):1196-1224. Free full-text PDF
AACE risk groups
Extreme risk: Target LDL-C <55 mg/dL via statin (non-HDL-C <80, apoB <70); use high-dose statin therapy, or statins combo w/ ezetimibe/PCSK9i/colesevelam/bempedoic acid if target not achieved.
• progressive ASCVD (eg, unstable angina despite LDL-C <70)
• established clinical CVD in DM, CKD stage 3/4, or heterozygous FH
• personal hx premature ASCVD: <55-yo male, <65-yo female
Very high: Target LDL-C <70 mg/dL (may consider even lower) via statin (non-HDL-C <100, apoB <80); use high-dose statin therapy, or statins combo w/ ezetimibe/PCSK9i/colesevelam/bempedoic acid if target not achieved.
• ACS (established/recent hospitalization); coronary, carotid dz, PVD
• Framingham 10-yr risk >20%
• DM or CKD stage 3/4, plus 1+ additional risk factor(s)
• Heterozygous FH
High: Target LDL-C <100 mg/dL (may consider even lower) via statin (non-HDL-C <130, apoB <90); start mod-dose statin therapy; if target not achieved, then high-dose statin, followed by statins combo w/ ezetimibe/colesevelam/bempedoic acid; consider PCSK9i as last resort.
• 2+ risk factors w/ Framingham 10-yr risk 10% to 20%
• ASCVD equivalent including DM or CKD stage 3/4, w/o other risk factors
Mod: Target LDL-C <100 mg/dL recommended (non-HDL-C <130, apoB <90); start mod-dose statin therapy; if target not achieved, then high-dose statin, followed by statins combo w/ ezetimibe/colesevelam/bempedoic acid; consider PCSK9i as last resort.
• ≤2 risk factors w/ Framingham 10-yr risk <10%
Low: Target LDL-C <130 mg/dL recommended (non-HDL-C <160); start lifestyle; if target not achieved, use mod-dose statin therapy, then high-dose statin, followed by statins combo w/ ezetimibe/colesevelam/bempedoic acid.
• 0 risk factors
AACE risk factors: If HDL-C >60 mg/dL, subtract 1 risk factor.
• Major risk: advancing age, ↑total/non-HDL-C/LDL-C, ↓HDL, DM, HTN, CKD, cigarette smoking, FHx ASCVD (eg, MI/SCD <55-yo male 1st-deg relative or <65-yo female 1st-deg relative)
• Additional: obesity/abdominal obesity, FHx ↑lipids, ↑small dense LDL-C, ↑apoB, ↑LDL particle concentration, fasting/postprandial ↑TG, PCOS, dyslipidemia triad (↑TG + ↓HDL + ↑small dense LDL-C)
• Nontraditional: ↑Lp(a), ↑clotting factors, ↑inflammatory markers (hs-CRP, Lp-PLA2), ↑homocysteine, ↑uric acid, ↑TG-rich remnants
Considerations in women
• Women at high risk (eg, Framingham or Reynolds 10-yr risk >20%): lipid-lowering (preferably statin) regardless of LDL-C; if ↓HDL-C or ↑non-HDL-C, add niacin or fibrate. Diet low in saturated/trans fat, <200 mg/day cholesterol.
• Women at intermediate risk (eg, Framingham 10-yr risk 10%-20%): lipid-lowering (preferably statin) if LDL-C >130. Once LDL-C goal is reached, if ↓HDL-C or ↑non-HDL-C, add niacin or fibrate and diet low in saturated/trans fat, cholesterol.
• Postmenopausal women: Don’t use HRT for dyslipidemia.
Diabetes
• T2DM is considered an ASCVD equivalent.
• T1DM-specific risks: These may ↑ ASCVD risk: albuminuria; insulin resistance/MetS; hs-CRP >3.0 mg/L; and in pts w/ T1DM onset >30 yo w/o nephropathy: started intensive control >5y after dx, T1DM >15-yr duration, poorly controlled A1C, or hx MI. If T1DM ≥15y w/ 2+ CV risk factors: treat as if T2DM for risk purposes.
FH: Consider PCSK9i combined w/ statin to ↓LDL-C. If homozygous FH doesn’t respond to PCSK9i: lomitapide and mipomerson, available via restricted distribution, may be useful. Unclear if PCSK9i is cost-effective in heterozygous FH pts.
Lifestyle: 30min mod-intense physical activity 4-6x/wk (≥10min/session) + musc strengthen 2x/wk. Low-cal, low–saturated/trans fat, low-chol diet w/ 5+ fruit/veg servings/day, grains (mostly whole), fish, lean meat; high fiber, ~2 g/day plant stanols/sterols. Smoking cessation.
AACE drug tx
• Statins preferred to lower LDL-C. Simvastatin 80 mg not recommended.
• ASCVD = ACS, MI hx, angina, coronary/other arterial revasc, stroke, TIA, atherosclerotic PAD (including aortic aneurysm)
• ↑blood glucose and/or ↑new-onset T2DM risk don’t outweigh statin benefit; DM risk is dose related, primarily occurs in MetS pts; may be less common w/ pravastatin, possibly pitavastatin. Rosuvastatin plasma levels may be higher in Asians.
• Statin alternatives. Ezetimibe can be used as mono-tx to lower LDL-C, apoB, esp if statin-intolerant. Don’t use PCSK9i as mono-tx except if statin intolerant. Unclear if PCSK9i is cost-effective in heterozygous FH or ASCVD pts.
• Combo tx. If LDL-C or non-HDL-C goals not met: Combine max-tolerated statin w/ ezetimibe, bile acid sequestrants (caution if ↑TG), bempedoic acid, or PCSK9i.
• Mixed dyslipidemia (↑LDL-C, ↑TG, ↓HDL-C): If high-dose mono-tx inadequate, may use combo, eg, statin + IPE, statin + niacin (but no clinical CV benefit from adding niacin if LDL-C already well controlled w/ statin), statin + fibrate, statin + bile acid sequestrant (caution if ↑TG), ezetimibe + fibrate, or ezetimibe + niacin.
• ↓HDL-C: If no other risk factors, don’t treat it. If additional risk factors, raise HDL-C to >40 mg/dL, at minimum (both sexes).
3 2023 ADA. 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2023. Diabetes Care. 2023. Jan 1;46(Suppl 1):S158-S190. Accessed 7/18/23
Secondary prevention
• DM + ASCVD, all ages:
◦ Use high-intensity statin added to lifestyle tx
◦ If high-intensity statin not tolerated, use max-tolerated statin dose
Lifestyle: wt ↓ if indicated; exercise; tailored nutrition intervention, eg, Mediterranean/DASH-style diet, ↓saturated & trans fat, ↑dietary n-3 fatty acids, viscous fiber, plant stanols/sterols.
Reasonable to start mod-/high-intensity statin for secondary prevention in ASCVD,1 after factoring risk-reduction potential, adverse effects, drug-drug interactions, health status, & pt preference; if already tolerating high-intensity statin, reasonable to continue, per ACC/AHA. AACE2 states that many older individuals benefit from lipid lowering; as do DM pts, per ADA.3 Heart-healthy lifestyle.1-3 Per ACC/AHA:1 - If very high-risk1 ASCVD: High-intensity/max-tolerated statin. If LDL-C ≥70 on max-tolerated statin, add-on ezetimibe reasonable. If LDL-C ≥70 (or non-HDL-C ≥100) despite max-tolerated statin + ezetimibe, reasonable to discuss add-on PCSK9i,1 per ACC/AHA; in pts w/ DM, target LDL-C reduction of ≥50% from baseline and LDL-C goal of <55, discuss add-on ezetimibe or PCSK9i (clinical CV benefit from adding ezetimibe or PCSK9i if target not achieved w/ max-tolerated statin),3 per ADA
- If not very high-risk1 ASCVD: Starting mod-/high-intensity statin (or continuing high-intensity if tolerating) is reasonable, after discussing net benefit
- If HFrEF from ischemic heart dz w/ reasonable life expectancy (eg, 3-5y) and not on statin: Consider mod-intensity statin, per ACC/AHA1
Footnotes 1 2018 AHA/ACC/etc. Grundy SM, 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. J Am Coll Cardiol. 2019 June 25;73(24):3210-3227. Accessed 2/2/21
ASCVD = ACS, MI hx, angina, coronary/other arterial revasc, stroke, TIA, atherosclerotic PAD (including aortic aneurysm).
Lifestyle. Wt loss prn. Exercise: Average of 40min mod-intense aerobic activity 3-4x/wk. Tobacco cessation. Diet: ↑vegetables, fruits, nuts, whole grains, legumes, lean veg/animal protein, fish. ↓trans fats, red/processed meat, refined carbs, sugar beverages.
Very high-risk ASCVD pt = Hx multiple major ASCVD events OR 1 major event + multiple high-risk conditions:
Major ASCVD events
• ACS in past 12mo
• Hx of MI
• Ischemic stroke hx
• Symptomatic PAD (claudication hx w/ ABI <0.85 or previous revasc/amputation)
High-risk conditions
• ≥65 yo
• Heterozygous FH
• CABG or PCI outside of major ASCVD event
• DM
• HTN
• CHF
• CKD (eGFR 15-59 mL/min/1.73m 2)
• Current smoker
• LDL-C persistently ≥100 despite max-tolerated statin + ezetimibe
Risk enhancers
• FHx of premature ASCVD
• Personal hx: CKD, preeclampsia, menopause <40 yo, metabolic syndrome (3 of these: ↑waist circ., TG >150 mg/dL, ↑BP, ↑glucose, HDL <40 men or <50 women), inflammatory dz (RA, psoriasis, chronic HIV), high-risk ethnicity (eg, South Asian)
• Labs. LDL-C persistently ≥160, TG persistently ≥175. If measured:
hs-CRP ≥2 mg/dL, Lp(a) ≥50 mg/dL, apoB ≥130 mg/dL
• ABI <0.9 (if measured)
Diabetes-specific risk enhancers: long-standing DM (≥10y T2, ≥20y T1), albuminuria (≥30 mcg albumin/mg Cr), eGFR <60 mL/min/1.73m 2, retinopathy, neuropathy, ABI <0.9.
PCSK9i = evolocumab or alirocumab. Discuss net benefit, long-term (>3y) safety uncertainty, cost. Economic value of PCSK9i at mid-2018 list price: low value for ASCVD, uncertain for 1° prevention in severe hypercholesterolemia, incl FH pts w/o clinical ASCVD on max-tolerated statin + ezetimibe.
2 2020 AACE/ACE. Handelsman Y, et al. Consensus Statement by the American Association of Clinical Endocrinologists and American College of Endocrinology on the Management of Dyslipidemia and Prevention of Cardiovascular Disease Algorithm – 2020 Executive Summary. Endocr Pract. 2020. Oct:26(10):1196-1224. Free full-text PDF
Lifestyle: 30min mod-intense physical activity 4-6x/wk (≥10min/session) + musc strengthen 2x/wk. Low-cal, low–saturated/trans fat, low-chol diet w/ 5+ fruit/veg servings/day, grains (mostly whole), fish, lean meat; high fiber, ~2 g/day plant stanols/sterols. Smoking cessation.
AACE drug tx
• Statins preferred to lower LDL-C. Simvastatin 80 mg not recommended.
• ASCVD = ACS, MI hx, angina, coronary/other arterial revasc, stroke, TIA, atherosclerotic PAD (including aortic aneurysm)
• ↑blood glucose and/or ↑new-onset T2DM risk don’t outweigh statin benefit; DM risk is dose related, primarily occurs in MetS pts; may be less common w/ pravastatin, possibly pitavastatin. Rosuvastatin plasma levels may be higher in Asians.
• Statin alternatives. Ezetimibe can be used as mono-tx to lower LDL-C, apoB, esp if statin-intolerant. Don’t use PCSK9i as mono-tx except if statin intolerant. Unclear if PCSK9i is cost-effective in heterozygous FH or ASCVD pts.
• Combo tx. If LDL-C or non-HDL-C goals not met: Combine max-tolerated statin w/ ezetimibe, bile acid sequestrants (caution if ↑TG), bempedoic acid, or PCSK9i.
• Mixed dyslipidemia (↑LDL-C, ↑TG, ↓HDL-C): If high-dose mono-tx inadequate, may use combo, eg, statin + IPE, statin + niacin (but no clinical CV benefit from adding niacin if LDL-C already well controlled w/ statin), statin + fibrate, statin + bile acid sequestrant (caution if ↑TG), ezetimibe + fibrate, or ezetimibe + niacin.
• ↓HDL-C: If no other risk factors, don’t treat it. If additional risk factors, raise HDL-C to >40 mg/dL, at minimum (both sexes).
Considerations in women
• Women at high risk (eg, Framingham or Reynolds 10-yr risk >20%): lipid-lowering (preferably statin) regardless of LDL-C; if ↓HDL-C or ↑non-HDL-C, add niacin or fibrate. Diet low in saturated/trans fat, <200 mg/day cholesterol.
• Women at intermediate risk (eg, Framingham 10-yr risk 10%-20%): lipid-lowering (preferably statin) if LDL-C >130. Once LDL-C goal is reached, if ↓HDL-C or ↑non-HDL-C, add niacin or fibrate and diet low in saturated/trans fat, cholesterol.
• Postmenopausal women: Don’t use HRT for dyslipidemia.
3 2023 ADA. 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2023. Diabetes Care. 2023. Jan 1;46(Suppl 1):S158-S190. Accessed 7/18/23
Secondary prevention
• DM + ASCVD, all ages:
◦ Use high-intensity statin added to lifestyle tx
◦ If high-intensity statin not tolerated, use max-tolerated statin dose
Lifestyle: wt ↓ if indicated; exercise; tailored nutrition intervention, eg, Mediterranean/DASH-style diet, ↓saturated & trans fat, ↑dietary n-3 fatty acids, viscous fiber, plant stanols/sterols.
-
Prompt high-intensity/max-tolerated statin for primary severe hypercholesterolemia, per ACC/AHA.1 AACE specifies target LDL-C based on risk2 and FH.2 ADA specifies recommendations for pts w/ DM.3 Heart-healthy lifestyle1-3 - 18-19 yo w/ persistent LDL-C ≥190: If inadequate response to 3- to 6-mo lifestyle trial, statin reasonable per ACC/AHA1
- 20-75 yo: High-intensity statin: atorvastatin 40 or 80 mg, rosuvastatin 20 or 40 mg. If LDL-C ↓<50% or LDL-C ≥100 while on max-tolerated statin, add-on ezetimibe reasonable, per ACC/AHA1
- >75 yo: Factor risk-reduction potential, adverse effects, drug interactions, health status, & pt preference in statin decision; if already tolerating high-intensity statin, reasonable to continue, per ACC/AHA.1 AACE states that many older people benefit from LDL-C lowering2
If inadequate response to max-tolerated statin + ezetimibe, AACE specifies additional combos;2 ACC/AHA specifies:1 - If LDL-C ↓ by <50% w/ fasting TG ≤300 mg/dL, age 20-75 yo: Consider add-on bile acid sequestrant
- If on-tx LDL-C ≥100 in pt w/ multiple risk factors:1 Consider add-on PCSK9i1
- If heterozygous FH w/ on-tx LDL-C ≥100, age 30-75 yo: Consider add-on PCSKi1
- If baseline LDL-C ≥220 w/ on-tx LDL-C ≥130, age 40-75 yo: Consider add-on PCSK9i1
- If inadequate control w/ drugs: LDL apheresis exists, refer to specialist
If HIV and 40-75 yo:4 - Initiate high-intensity (≥50% LDL-C–lowering) statin tx at max tolerated dose:
◦ atorvastatin 40-80 mg qd
◦ rosuvastatin 20-40 mg qd - Atorvastatin and rosuvastatin interact w/ ritonavir- and cobicistat-boosted ARVs.
- If pregnant: Defer statin tx initiation until after pregnancy in pts at low to intermediate ASCVD risk. If on statin tx, discontinue. Breastfeeding is not recommended while on statin tx.
If HIV and <40 yo:4 - Data are insufficient to recommend for or against statin tx as 1° ASCVD prevention. In the general population, lifestyle modifications are recommended for people <40 yo, w/ statins considered only in select populations. See AHA/ACC/etc. guidance in footnote 1.
Footnotes 1 2018 AHA/ACC/etc. Grundy SM, 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. J Am Coll Cardiol. 2019 June 25;73(24):3210-3227. Accessed 2/2/21
Lifestyle. Wt loss prn. Exercise: Average of 40min mod-intense aerobic activity 3-4x/wk. Tobacco cessation. Diet: ↑vegetables, fruits, nuts, whole grains, legumes, lean veg/animal protein, fish. ↓trans fats, red/processed meat, refined carbs, sugar beverages.
10-yr ASCVD risk calc based on pooled cohort equation. Best validated in non-Hispanic White/Black pts 40-75 yo.
High-risk conditions
• ≥65 yo
• Heterozygous FH
• CABG or PCI outside of major ASCVD event
• DM
• HTN
• CHF
• CKD (eGFR 15-59 mL/min/1.73m 2)
• Current smoker
• LDL-C persistently ≥100 despite max-tolerated statin + ezetimibe
Risk enhancers
• FHx of premature ASCVD
• Personal hx: CKD, preeclampsia, menopause <40 yo, metabolic syndrome (3 of these: ↑waist circ., TG >150 mg/dL, ↑BP, ↑glucose, HDL <40 men or <50 women), inflammatory dz (RA, psoriasis, chronic HIV), high-risk ethnicity (eg, South Asian)
• Labs. LDL-C persistently ≥160, TG persistently ≥175. If measured:
hs-CRP ≥2 mg/dL, Lp(a) ≥50 mg/dL, apoB ≥130 mg/dL
• ABI <0.9 (if measured)
Diabetes-specific risk enhancers: long-standing DM (≥10y T2, ≥20y T1), albuminuria (≥30 mcg albumin/mg Cr), eGFR <60 mL/min/1.73m 2, retinopathy, neuropathy, ABI <0.9.
PCSK9i = evolocumab or alirocumab. Discuss net benefit, long-term (>3y) safety uncertainty, cost. PCSK9i of uncertain economic value at mid-2018 list price, including for FH pts w/o clinical ASCVD on max-tolerated statin + ezetimibe.
2 2020 AACE/ACE. Handelsman Y, et al. Consensus Statement by the American Association of Clinical Endocrinologists and American College of Endocrinology on the Management of Dyslipidemia and Prevention of Cardiovascular Disease Algorithm – 2020 Executive Summary. Endocr Pract. 2020. Oct:26(10):1196-1224. Free full-text PDF
AACE risk groups
Extreme risk: Target LDL-C <55 mg/dL via statin (non-HDL-C <80, apoB <70); use high-dose statin therapy, or statins combo w/ ezetimibe/PCSK9i/colesevelam/bempedoic acid if target not achieved.
• progressive ASCVD (eg, unstable angina despite LDL-C <70)
• established clinical CVD in DM, CKD stage 3/4, or heterozygous FH
• personal hx premature ASCVD: <55-yo male, <65-yo female
Very high: Target LDL-C <70 mg/dL (may consider even lower) via statin (non-HDL-C <100, apoB <80); use high-dose statin therapy, or statins combo w/ ezetimibe/PCSK9i/colesevelam/bempedoic acid if target not achieved.
• ACS (established/recent hospitalization); coronary, carotid dz, PVD
• Framingham 10-yr risk >20%
• DM or CKD stage 3/4, plus 1+ additional risk factor(s)
• Heterozygous FH
High: Target LDL-C <100 mg/dL (may consider even lower) via statin (non-HDL-C <130, apoB <90); start mod-dose statin therapy; if target not achieved, then high-dose statin, followed by statins combo w/ ezetimibe/colesevelam/bempedoic acid; consider PCSK9i as last resort.
• 2+ risk factors w/ Framingham 10-yr risk 10% to 20%
• ASCVD equivalent including DM or CKD stage 3/4, w/o other risk factors
Mod: Target LDL-C <100 mg/dL recommended (non-HDL-C <130, apoB <90); start mod-dose statin therapy; if target not achieved, then high-dose statin, followed by statins combo w/ ezetimibe/colesevelam/bempedoic acid; consider PCSK9i as last resort.
• ≤2 risk factors w/ Framingham 10-yr risk <10%
Low: Target LDL-C <130 mg/dL recommended (non-HDL-C <160); start lifestyle; if target not achieved, use mod-dose statin therapy, then high-dose statin, followed by statins combo w/ ezetimibe/colesevelam/bempedoic acid.
• 0 risk factors
AACE risk factors: If HDL-C >60 mg/dL, subtract 1 risk factor.
• Major risk: advancing age, ↑total/non-HDL-C/LDL-C, ↓HDL, DM, HTN, CKD, cigarette smoking, FHx ASCVD (eg, MI/SCD <55-yo male 1st-deg relative or <65-yo female 1st-deg relative)
• Additional: obesity/abdominal obesity, FHx ↑lipids, ↑small dense LDL-C, ↑apoB, ↑LDL particle concentration, fasting/postprandial ↑TG, PCOS, dyslipidemia triad (↑TG + ↓HDL + ↑small dense LDL-C)
• Nontraditional: ↑Lp(a), ↑clotting factors, ↑inflammatory markers (hs-CRP, Lp-PLA2), ↑homocysteine, ↑uric acid, ↑TG-rich remnants
AACE drug tx
• Statins preferred to lower LDL-C. Simvastatin 80 mg not recommended.
• ASCVD = ACS, MI hx, angina, coronary/other arterial revasc, stroke, TIA, atherosclerotic PAD (including aortic aneurysm)
• ↑blood glucose and/or ↑new-onset T2DM risk don’t outweigh statin benefit; DM risk is dose related, primarily occurs in MetS pts; may be less common w/ pravastatin, possibly pitavastatin. Rosuvastatin plasma levels may be higher in Asians.
• Statin alternatives. Ezetimibe can be used as mono-tx to lower LDL-C, apoB, esp if statin-intolerant. Don’t use PCSK9i as mono-tx except if statin intolerant. Unclear if PCSK9i is cost-effective in heterozygous FH or ASCVD pts.
• Combo tx. If LDL-C or non-HDL-C goals not met: Combine max-tolerated statin w/ ezetimibe, bile acid sequestrants (caution if ↑TG), bempedoic acid, or PCSK9i.
• Mixed dyslipidemia (↑LDL-C, ↑TG, ↓HDL-C): If high-dose mono-tx inadequate, may use combo, eg, statin + IPE, statin + niacin (but no clinical CV benefit from adding niacin if LDL-C already well controlled w/ statin), statin + fibrate, statin + bile acid sequestrant (caution if ↑TG), ezetimibe + fibrate, or ezetimibe + niacin.
• ↓HDL-C: If no other risk factors, don’t treat it. If additional risk factors, raise HDL-C to >40 mg/dL, at minimum (both sexes).
Considerations in women
• Women at high risk (eg, Framingham or Reynolds 10-yr risk >20%): lipid-lowering (preferably statin) regardless of LDL-C; if ↓HDL-C or ↑non-HDL-C, add niacin or fibrate. Diet low in saturated/trans fat, <200 mg/day cholesterol.
• Women at intermediate risk (eg, Framingham 10-yr risk 10%-20%): lipid-lowering (preferably statin) if LDL-C >130. Once LDL-C goal is reached, if ↓HDL-C or ↑non-HDL-C, add niacin or fibrate and diet low in saturated/trans fat, cholesterol.
• Postmenopausal women: Don’t use HRT for dyslipidemia.
Diabetes
• T2DM is considered an ASCVD equivalent.
• T1DM-specific risks: These may ↑ ASCVD risk: albuminuria; insulin resistance/MetS; hs-CRP >3.0 mg/L; and in pts w/ T1DM onset >30 yo w/o nephropathy: started intensive control >5y after dx, T1DM >15-yr duration, poorly controlled A1C, or hx MI. If T1DM ≥15y w/ 2+ CV risk factors: treat as if T2DM for risk purposes.
FH: Consider PCSK9i combined w/ statin to ↓LDL-C. If homozygous FH doesn’t respond to PCSK9i: lomitapide and mipomersen, available via restricted distribution, may be useful. Unclear if PCSK9i is cost-effective in heterozygous FH pts.
Lifestyle: 30min mod-intense physical activity 4-6x/wk (≥10min/session) + musc strengthen 2x/wk. Low-cal, low–saturated/trans fat, low-chol diet w/ 5+ fruit/veg servings/day, grains (mostly whole), fish, lean meat; high fiber, ~2 g/day plant stanols/sterols. Smoking cessation.
3 2023 ADA. 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2023. Diabetes Care. 2023. Jan 1;46(Suppl 1):S158-S190. Accessed 7/18/23
Primary prevention
• <40 yo and/or T1DM: Discuss risks/benefits w/ pts w/ other ASCVD risk factors, consider mod-intensity statin; little trial evidence exists for pts <40 yo w/ T2DM or pts of any age w/ T1DM; consider similar statin tx approaches for pts w/ T1DM and T2DM, esp in presence of CVD risk factors.
• 20-39 yo w/ DM plus additional ASCVD risk factors: Starting statin may be reasonable.
• 40-75 yo w/ DM w/o ASCVD: mod-intensity statin.
• 40-75 yo w/ DM at higher CVD risk, esp w/ multiple ASCVD risk factors: Use high-intensity statin to ↓ LDL-C by ≥50%; adding ezetimibe or PCSK9i to max-tolerated statin may be reasonable in pts w/ an LDL-C ≥70 mg/dL
• ≥75 yo w/ DM: mod-intensity statin; however, routine re-eval could down-titrate dose as needed
• >75 yo w/ DM: If already on statin, reasonable to continue. Otherwise, after discussing net benefits and risks, it may be reasonable to start statin.
Lifestyle: wt ↓ if indicated; exercise; tailored nutrition intervention, eg, Mediterranean/DASH-style diet, ↓saturated & trans fat, ↑dietary n-3 fatty acids, viscous fiber, plant stanols/sterols.
4 DHHS 2024. U.S. Department of Health and Human Services Panel for the Use of Antiretroviral Agents in Adults and Adolescents with HIV, American College of Cardiology, American Heart Association, and HIV Medicine Association. Recommendations for the Use of Statin Therapy as Primary Prevention of Atherosclerotic Cardiovascular Disease in People with HIV. Clinicalinfo.HIV.gov. February 27, 2024. Accessed June 25, 2024. Full-text PDF
Factor age, DM-specific risk factors, & other ASCVD risks in LDL-lowering approach for primary prevention.1 ADA considers T1 and T2 similarly, esp in presence of CVD risk factors.2 AACE considers DM to be an ASCVD equivalent;3 target LDL-C <70 if very high risk, <100 if high risk.3 Heart-healthy lifestyle1-3 - 20-39 yo: May be reasonable to start mod-intensity statin if long-standing DM (≥10y T2, ≥20y T1) and/or if major CVD risk factor(s),1 albuminuria (≥30 mcg albumin/mg Cr), eGFR <60 mL/min/1.73m2, retinopathy, neuropathy, ABI <0.9, per ACC/AHA.1 ADA considers statins reasonable if additional ASCVD risk factors2
- 40-75 yo w/ LDL-C 70-189: Mod-intensity statin indicated. If higher risk, esp pts w/ multiple ASCVD risk factors1 or 50-75 yo: high-intensity statin reasonable to ↓ LDL-C by ≥50% (if inadequate, add ezetimibe; if high-intensity not tolerated, use mod-intensity + ezetimibe). If 10-yr ASCVD risk ≥20%, may be reasonable to add ezetimibe to max-tolerated statin to ↓ LDL-C by ≥50%, per ACC/AHA1
- 40-75 yo w/ DM at higher CVD risk, esp w/ multiple ASCVD risk factors: Use high-intensity statin to ↓ LDL-C by ≥50%; adding ezetimibe or PCSK9i to max-tolerated statin may be reasonable in pts w/ an LDL-C ≥70 mg/dL
- >75 yo: If already on mod-/high-intensity statin, reasonable to continue. Otherwise, may be reasonable to start statin after discussing net benefits, risks, etc, per ACC/AHA1
- >75 yo w/ DM: If already on statin, reasonable to continue. Otherwise, after discussing net benefits and risks, it may be reasonable to start statin,2 per ADA.
Select statin1,2 if indicated based on risk, per ACC/AHA and ADA: If HIV and 40-75 yo:3 - Initiate at least moderate-intensity (30%-49% LDL-C–lowering) statin tx:
◦ pitavastatin 4 mg qd [AI]
◦ atorvastatin 20 mg qd [AII]
◦ rosuvastatin 10 mg qd [AII]
- Perform further risk assessment to consider using a high-intensity (≥50% LDL-C–lowering) statin:
◦ atorvastatin 40-80 mg qd
◦ rosuvastatin 20-40 mg qd - Atorvastatin and rosuvastatin interact w/ ritonavir- and cobicistat-boosted ARVs.
- If pregnant: Defer statin tx initiation until after pregnancy in pts at low to intermediate ASCVD risk. If on statin tx, discontinue. Breastfeeding is not recommended while on statin tx.
If HIV and <40 yo:3 - Data are insufficient to recommend for or against statin tx as 1° ASCVD prevention. In the general population, lifestyle modifications are recommended for people <40 yo, w/ statins considered only in select populations. See AHA/ACC/etc. guidance in footnote 1.
Footnotes 1 2018 AHA/ACC/etc. Grundy SM, 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. J Am Coll Cardiol. 2019 June 25;73(24):3210-3227. Accessed 2/2/21
Lifestyle. Wt loss prn. Exercise: Average of 40min mod-intense aerobic activity 3-4x/wk. Tobacco cessation. Diet: ↑vegetables, fruits, nuts, whole grains, legumes, lean veg/animal protein, fish. ↓trans fats, red/processed meat, refined carbs, sugar beverages.
10-yr ASCVD risk calc based on pooled cohort equation. Best validated in non-Hispanic White/Black pts 40-75 yo.
High-risk conditions
• ≥65 yo
• Heterozygous FH
• CABG or PCI outside of major ASCVD event
• DM
• HTN
• CHF
• CKD (eGFR 15-59 mL/min/1.73m 2)
• Current smoker
• LDL-C persistently ≥100 despite max-tolerated statin + ezetimibe
Risk enhancers
• FHx of premature ASCVD
• Personal hx: CKD, preeclampsia, menopause <40 yo, metabolic syndrome (3 of these: ↑waist circ., TG >150 mg/dL, ↑BP, ↑glucose, HDL <40 men or <50 women), inflammatory dz (RA, psoriasis, chronic HIV), high-risk ethnicity (eg, South Asian)
• Labs. LDL-C persistently ≥160, TG persistently ≥175. If measured:
hs-CRP ≥2 mg/dL, Lp(a) ≥50 mg/dL, apoB ≥130 mg/dL
• ABI <0.9 (if measured)
Diabetes-specific risk enhancers: long-standing DM (≥10y T2, ≥20y T1), albuminuria (≥30 mcg albumin/mg Cr), eGFR <60 mL/min/1.73m 2, retinopathy, neuropathy, ABI <0.9.
2 2023 ADA. 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2023. Diabetes Care. 2023. Jan 1;46(Suppl 1):S158-S190. Accessed 7/18/23
Primary prevention
• <40 yo and/or T1DM: Discuss risks/benefits w/ pts w/ other ASCVD risk factors, consider mod-intensity statin; little trial evidence exists for pts <40 yo w/ T2DM or pts of any age w/ T1DM; consider similar statin tx approaches for pts w/ T1DM and T2DM, esp in presence of CVD risk factors.
• 20-39 yo w/ DM plus additional ASCVD risk factors: Starting statin may be reasonable.
• 40-75 yo w/ DM w/o ASCVD: mod-intensity statin.
• 40-75 yo w/ DM at higher CVD risk, esp w/ multiple ASCVD risk factors: Use high-intensity statin to ↓ LDL-C by ≥50%; adding ezetimibe or PCSK9i to max-tolerated statin may be reasonable in pts w/ an LDL-C ≥70 mg/dL.
• ≥75 yo w/ DM: mod-intensity statin; however, routine re-eval could down-titrate dose as needed.
• >75 yo w/ DM: If already on statin, reasonable to continue. Otherwise, after discussing net benefits and risks, it may be reasonable to start statin.
Lifestyle: wt ↓ if indicated; exercise; tailored nutrition intervention, eg, Mediterranean/DASH-style diet, ↓saturated & trans fat, ↑dietary n-3 fatty acids, viscous fiber, plant stanols/sterols.
Statin dosing
• High-intensity statin (daily dose): atorvastatin 40-80 mg, rosuvastatin 20-40 mg.
• Mod-intensity statin (daily dose): atorvastatin 10-20 mg, rosuvastatin 5-10 mg, simvastatin 20-40 mg, pravastatin 40-80 mg, lovastatin 40 mg, fluvastatin XL 80 mg, pitavastatin 1-4 mg.
• Combos. Statins may be combined w/ ezetimibe or PCSK9i; however, based on evidence, statin combined w/ fibrates or niacin not generally recommended.
3 2020 AACE/ACE. Handelsman Y, et al. Consensus Statement by the American Association of Clinical Endocrinologists and American College of Endocrinology on the Management of Dyslipidemia and Prevention of Cardiovascular Disease Algorithm – 2020 Executive Summary. Endocr Pract. 2020. Oct:26(10):1196-1224. Free full-text PDF
Diabetes
• T2DM is considered an ASCVD equivalent.
• T1DM-specific risks: These may ↑ ASCVD risk: albuminuria; insulin resistance/MetS; hs-CRP >3.0 mg/L; and in pts w/ T1DM onset >30 yo w/o nephropathy: started intensive control >5y after dx, T1DM >15-yr duration, poorly controlled A1C, or hx MI. If T1DM ≥15y w/ 2+ CV risk factors: treat as if T2DM for risk purposes.
AACE risk groups
Extreme risk: Target LDL-C <55 mg/dL via statin (non-HDL-C <80, apoB <70); use high-dose statin therapy, or statins combo w/ ezetimibe/PCSK9i/colesevelam/bempedoic acid if target not achieved.
• progressive ASCVD (eg, unstable angina despite LDL-C <70)
• established clinical CVD in DM, CKD stage 3/4, or heterozygous FH
• personal hx premature ASCVD: <55-yo male, <65-yo female
Very high: Target LDL-C <70 mg/dL (may consider even lower) via statin (non-HDL-C <100, apoB <80); use high-dose statin therapy, or statins combo w/ ezetimibe/PCSK9i/colesevelam/bempedoic acid if target not achieved.
• ACS (established/recent hospitalization); coronary, carotid dz, PVD
• Framingham 10-yr risk >20%
• DM or CKD stage 3/4, plus 1+ additional risk factor(s)
• Heterozygous FH
High: Target LDL-C <100 mg/dL (may consider even lower) via statin (non-HDL-C <130, apoB <90); start mod-dose statin therapy; if target not achieved, then high-dose statin, followed by statins combo w/ ezetimibe/colesevelam/bempedoic acid; consider PCSK9i as last resort.
• 2+ risk factors w/ Framingham 10-yr risk 10% to 20%
• ASCVD equivalent including DM or CKD stage 3/4, w/o other risk factors
Mod: Target LDL-C <100 mg/dL recommended (non-HDL-C <130, apoB <90); start mod-dose statin therapy; if target not achieved, then high-dose statin, followed by statins combo w/ ezetimibe/colesevelam/bempedoic acid; consider PCSK9i as last resort.
• ≤2 risk factors w/ Framingham 10-yr risk <10%
Low: Target LDL-C <130 mg/dL recommended (non-HDL-C <160); start lifestyle; if target not achieved, use mod-dose statin therapy, then high-dose statin, followed by statins combo w/ ezetimibe/colesevelam/bempedoic acid.
• 0 risk factors
AACE risk factors: If HDL-C >60 mg/dL, subtract 1 risk factor.
• Major risk: advancing age, ↑total/non-HDL-C/LDL-C, ↓HDL, DM, HTN, CKD, cigarette smoking, FHx ASCVD (eg, MI/SCD <55-yo male 1st-deg relative or <65-yo female 1st-deg relative)
• Additional: obesity/abdominal obesity, FHx ↑lipids, ↑small dense LDL-C, ↑apoB, ↑LDL particle concentration, fasting/postprandial ↑TG, PCOS, dyslipidemia triad (↑TG + ↓HDL + ↑small dense LDL-C)
• Nontraditional: ↑Lp(a), ↑clotting factors, ↑inflammatory markers (hs-CRP, Lp-PLA2), ↑homocysteine, ↑uric acid, ↑TG-rich remnants
AACE drug tx
• Statins preferred to lower LDL-C. Simvastatin 80 mg not recommended.
• ASCVD = ACS, MI hx, angina, coronary/other arterial revasc, stroke, TIA, atherosclerotic PAD (including aortic aneurysm)
• ↑blood glucose and/or ↑new-onset T2DM risk don’t outweigh statin benefit; DM risk is dose related, primarily occurs in MetS pts; may be less common w/ pravastatin, possibly pitavastatin. Rosuvastatin plasma levels may be higher in Asians.
• Statin alternatives. Ezetimibe can be used as mono-tx to lower LDL-C, apoB, esp if statin-intolerant. Don’t use PCSK9i as mono-tx except if statin intolerant. Unclear if PCSK9i is cost-effective in heterozygous FH or ASCVD pts.
• Combo tx. If LDL-C or non-HDL-C goals not met: Combine max-tolerated statin w/ ezetimibe, bile acid sequestrants (caution if ↑TG), bempedoic acid, or PCSK9i.
• Mixed dyslipidemia (↑LDL-C, ↑TG, ↓HDL-C): If high-dose mono-tx inadequate, may use combo, eg, statin + IPE, statin + niacin (but no clinical CV benefit from adding niacin if LDL-C already well controlled w/ statin), statin + fibrate, statin + bile acid sequestrant (caution if ↑TG), ezetimibe + fibrate, or ezetimibe + niacin.
• ↓HDL-C: If no other risk factors, don’t treat it. If additional risk factors, raise HDL-C to >40 mg/dL, at minimum (both sexes).
Considerations in women
• Women at high risk (eg, Framingham or Reynolds 10-yr risk >20%): lipid-lowering (preferably statin) regardless of LDL-C; if ↓HDL-C or ↑non-HDL-C, add niacin or fibrate. Diet low in saturated/trans fat, <200 mg/day cholesterol.
• Women at intermediate risk (eg, Framingham 10-yr risk 10%-20%): lipid-lowering (preferably statin) if LDL-C >130. Once LDL-C goal is reached, if ↓HDL-C or ↑non-HDL-C, add niacin or fibrate and diet low in saturated/trans fat, cholesterol.
• Postmenopausal women: Don’t use HRT for dyslipidemia.
Lifestyle: 30min mod-intense physical activity 4-6x/wk (≥10min/session) + musc strengthen 2x/wk. Low-cal, low–saturated/trans fat, low-chol diet w/ 5+ fruit/veg servings/day, grains (mostly whole), fish, lean meat; high fiber, ~2 g/day plant stanols/sterols. Smoking cessation.
3 DHHS 2024. U.S. Department of Health and Human Services Panel for the Use of Antiretroviral Agents in Adults and Adolescents with HIV, American College of Cardiology, American Heart Association, and HIV Medicine Association. Recommendations for the Use of Statin Therapy as Primary Prevention of Atherosclerotic Cardiovascular Disease in People with HIV. Clinicalinfo.HIV.gov. February 27, 2024. Accessed June 25, 2024. Full-text PDF
Heart-healthy lifestyle1,2 for primary prevention; consider statins for select pts, per ACC/AHA:1 - If adolescent w/ obesity-related lipid disorder: Intensify lifestyle (↓calories, 30-60min mod-vigorous aerobic activity most days) beyond usual obesity recommendations. Lifestyle counseling beneficial for ↓ LDL-C
- If LDL-C ≥160 w/ clinical FH (by genotype or phenotypic presentation): Lifestyle1 trial x3-6mo; if inadequate response, statin reasonable in light of shared decision-making/counseling
- If FHx is concerning or ↑Lp(a): May consider statins in context of informed shared decision-making/counseling
If statin1 required, base intensity on cholesterol level, pt preference, etc - High-intensity (≥50% LDL-C lowering): atorvastatin 40 or 80 mg, rosuvastatin 20 or 40 mg
- Mod-intensity (30%-49% LDL-C lowering): atorvastatin 10 or 20 mg, rosuvastatin 5 or 10 mg, simvastatin 20-40 mg, pravastatin 40 or 80 mg, lovastatin 40 or 80 mg, fluvastatin XL 80 mg, fluvastatin 40 mg bid, pitavastatin 1-4 mg
- Low-intensity (<30% LDL-C lowering): simvastatin 10 mg, pravastatin 10-20 mg, lovastatin 20 mg, fluvastatin 20-40 mg
If HIV:3 - Data are insufficient to recommend for or against statin tx as 1° ASCVD prevention. In the general population, lifestyle modifications are recommended for people <40 yo, w/ statins considered only in select populations. See AHA/ACC/etc. guidance in footnote 1.
Footnotes 1 2018 AHA/ACC/etc. Grundy SM, 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. J Am Coll Cardiol. 2019 June 25;73(24):3210-3227. Accessed 2/2/21
Lifestyle. Wt loss prn. Exercise: Average of 40min mod-intense aerobic activity 3-4x/wk. Tobacco cessation. Diet: ↑vegetables, fruits, nuts, whole grains, legumes, lean veg/animal protein, fish. ↓trans fats, red/processed meat, refined carbs, sugar beverages.
2 2020 AACE/ACE. Handelsman Y, et al. Consensus Statement by the American Association of Clinical Endocrinologists and American College of Endocrinology on the Management of Dyslipidemia and Prevention of Cardiovascular Disease Algorithm – 2020 Executive Summary. Endocr Pract. 2020. Oct:26(10):1196-1224. Free full-text PDF
Lifestyle: 30min mod-intense physical activity 4-6x/wk (≥10min/session) + musc strengthen 2x/wk. Low-cal, low–saturated/trans fat, low-chol diet w/ 5+ fruit/veg servings/day, grains (mostly whole), fish, lean meat; high fiber, ~2 g/day plant stanols/sterols. Smoking cessation.
AACE drug tx
• Statins preferred to lower LDL-C. Simvastatin 80 mg not recommended.
• ASCVD = ACS, MI hx, angina, coronary/other arterial revasc, stroke, TIA, atherosclerotic PAD (including aortic aneurysm)
• ↑blood glucose and/or ↑new-onset T2DM risk don’t outweigh statin benefit; DM risk is dose related, primarily occurs in MetS pts; may be less common w/ pravastatin, possibly pitavastatin. Rosuvastatin plasma levels may be higher in Asians.
• Statin alternatives. Ezetimibe can be used as mono-tx to lower LDL-C, apoB, esp if statin-intolerant. Don’t use PCSK9i as mono-tx except if statin intolerant. Unclear if PCSK9i is cost-effective in heterozygous FH or ASCVD pts.
• Combo tx. If LDL-C or non-HDL-C goals not met: Combine max-tolerated statin w/ ezetimibe, bile acid sequestrants (caution if ↑TG), bempedoic acid, or PCSK9i.
• Mixed dyslipidemia (↑LDL-C, ↑TG, ↓HDL-C): If high-dose mono-tx inadequate, may use combo, eg, statin + IPE, statin + niacin (but no clinical CV benefit from adding niacin if LDL-C already well controlled w/ statin), statin + fibrate, statin + bile acid sequestrant (caution if ↑TG), ezetimibe + fibrate, or ezetimibe + niacin.
• ↓HDL-C: If no other risk factors, don’t treat it. If additional risk factors, raise HDL-C to >40 mg/dL, at minimum (both sexes).
Considerations in women
• Women at high risk (eg, Framingham or Reynolds 10-yr risk >20%): lipid-lowering (preferably statin) regardless of LDL-C; if ↓HDL-C or ↑non-HDL-C, add niacin or fibrate. Diet low in saturated/trans fat, <200 mg/day cholesterol.
• Women at intermediate risk (eg, Framingham 10-yr risk 10%-20%): lipid-lowering (preferably statin) if LDL-C >130. Once LDL-C goal is reached, if ↓HDL-C or ↑non-HDL-C, add niacin or fibrate and diet low in saturated/trans fat, cholesterol.
3 DHHS 2024. U.S. Department of Health and Human Services Panel for the Use of Antiretroviral Agents in Adults and Adolescents with HIV, American College of Cardiology, American Heart Association, and HIV Medicine Association. Recommendations for the Use of Statin Therapy as Primary Prevention of Atherosclerotic Cardiovascular Disease in People with HIV. Clinicalinfo.HIV.gov. February 27, 2024. Accessed June 25, 2024. Full-text PDF
Estimate lifetime risk (calc,1 risks,1 risk-enhancing factors1) to determine primary prevention approach. AACE specifies target LDL-C based on risk.2 Heart-healthy lifestyle;1,2 consider statin in select pts. No RCT data available on CAC for this age group. Per ACC/AHA: - If metabolic syndrome (3 of these: ↑waist circ., TG >150 mg/dL, ↑BP, ↑glucose, HDL <40 men or <50 women): Lifestyle is primary
- If LDL-C 160-189 w/ FHx of premature CVD: Consider statin
If statin1 required due to risk, base intensity on cholesterol level, pt preference, etc - High-intensity (≥50% LDL-C lowering): atorvastatin 40 or 80 mg, rosuvastatin 20 or 40 mg
- Mod-intensity (30%-49% LDL-C lowering): atorvastatin 10 or 20 mg, rosuvastatin 5 or 10 mg, simvastatin 20-40 mg, pravastatin 40 or 80 mg, lovastatin 40 or 80 mg, fluvastatin XL 80 mg, fluvastatin 40 mg bid, pitavastatin 1-4 mg
- Low-intensity (<30% LDL-C lowering): simvastatin 10 mg, pravastatin 10-20 mg, lovastatin 20 mg, fluvastatin 20-40 mg
If HIV:3 - Data are insufficient to recommend for or against statin tx as 1° ASCVD prevention. In the general population, lifestyle modifications are recommended for people <40 yo, w/ statins considered only in select populations. See AHA/ACC/etc. guidance in footnote 1.
Footnotes 1 2018 AHA/ACC/etc. Grundy SM, 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. J Am Coll Cardiol. 2019 June 25;73(24):3210-3227. Accessed 2/2/21
10-yr ASCVD risk calc based on pooled cohort equation. Best validated in non-Hispanic White/Black pts 40-75 yo.
High-risk conditions
• ≥65 yo
• Heterozygous FH
• CABG or PCI outside of major ASCVD event
• DM
• HTN
• CHF
• CKD (eGFR 15-59 mL/min/1.73m 2)
• Current smoker
• LDL-C persistently ≥100 despite max-tolerated statin + ezetimibe
Risk enhancers
• FHx of premature ASCVD
• Personal hx: CKD, preeclampsia, menopause <40 yo, metabolic syndrome (3 of these: ↑waist circ., TG >150 mg/dL, ↑BP, ↑glucose, HDL <40 men or <50 women), inflammatory dz (RA, psoriasis, chronic HIV), high-risk ethnicity (eg, South Asian)
• Labs. LDL-C persistently ≥160, TG persistently ≥175. If measured:
hs-CRP ≥2 mg/dL, Lp(a) ≥50 mg/dL, apoB ≥130 mg/dL
• ABI <0.9 (if measured)
Lifestyle. Wt loss prn. Exercise: Average of 40min mod-intense aerobic activity 3-4x/wk. Tobacco cessation. Diet: ↑vegetables, fruits, nuts, whole grains, legumes, lean veg/animal protein, fish. ↓trans fats, red/processed meat, refined carbs, sugar beverages.
2 2020 AACE/ACE. Handelsman Y, et al. Consensus Statement by the American Association of Clinical Endocrinologists and American College of Endocrinology on the Management of Dyslipidemia and Prevention of Cardiovascular Disease Algorithm – 2020 Executive Summary. Endocr Pract. 2020. Oct:26(10):1196-1224. Free full-text PDF
AACE risk groups
Extreme risk: Target LDL-C <55 mg/dL via statin (non-HDL-C <80, apoB <70); use high-dose statin therapy, or statins combo w/ ezetimibe/PCSK9i/colesevelam/bempedoic acid if target not achieved.
• progressive ASCVD (eg, unstable angina despite LDL-C <70)
• established clinical CVD in DM, CKD stage 3/4, or heterozygous FH
• personal hx premature ASCVD: <55-yo male, <65-yo female
Very high: Target LDL-C <70 mg/dL (may consider even lower) via statin (non-HDL-C <100, apoB <80); use high-dose statin therapy, or statins combo w/ ezetimibe/PCSK9i/colesevelam/bempedoic acid if target not achieved.
• ACS (established/recent hospitalization); coronary, carotid dz, PVD
• Framingham 10-yr risk >20%
• DM or CKD stage 3/4, plus 1+ additional risk factor(s)
• Heterozygous FH
High: Target LDL-C <100 mg/dL (may consider even lower) via statin (non-HDL-C <130, apoB <90); start mod-dose statin therapy; if target not achieved, then high-dose statin, followed by statins combo w/ ezetimibe/colesevelam/bempedoic acid; consider PCSK9i as last resort.
• 2+ risk factors w/ Framingham 10-yr risk 10% to 20%
• ASCVD equivalent including DM or CKD stage 3/4, w/o other risk factors
Mod: Target LDL-C <100 mg/dL recommended (non-HDL-C <130, apoB <90); start mod-dose statin therapy; if target not achieved, then high-dose statin, followed by statins combo w/ ezetimibe/colesevelam/bempedoic acid; consider PCSK9i as last resort.
• ≤2 risk factors w/ Framingham 10-yr risk <10%
Low: Target LDL-C <130 mg/dL recommended (non-HDL-C <160); start lifestyle; if target not achieved, use mod-dose statin therapy, then high-dose statin, followed by statins combo w/ ezetimibe/colesevelam/bempedoic acid.
• 0 risk factors
AACE risk factors: If HDL-C >60 mg/dL, subtract 1 risk factor.
• Major risk: advancing age, ↑total/non-HDL-C/LDL-C, ↓HDL, DM, HTN, CKD, cigarette smoking, FHx ASCVD (eg, MI/SCD <55-yo male 1st-deg relative or <65-yo female 1st-deg relative)
• Additional: obesity/abdominal obesity, FHx ↑lipids, ↑small dense LDL-C, ↑apoB, ↑LDL particle concentration, fasting/postprandial ↑TG, PCOS, dyslipidemia triad (↑TG + ↓HDL + ↑small dense LDL-C)
• Nontraditional: ↑Lp(a), ↑clotting factors, ↑inflammatory markers (hs-CRP, Lp-PLA2), ↑homocysteine, ↑uric acid, ↑TG-rich remnants
Considerations in women
• Women at high risk (eg, Framingham or Reynolds 10-yr risk >20%): lipid-lowering (preferably statin) regardless of LDL-C; if ↓HDL-C or ↑non-HDL-C, add niacin or fibrate. Diet low in saturated/trans fat, <200 mg/day cholesterol.
• Women at intermediate risk (eg, Framingham 10-yr risk 10%-20%): lipid-lowering (preferably statin) if LDL-C >130. Once LDL-C goal is reached, if ↓HDL-C or ↑non-HDL-C, add niacin or fibrate and diet low in saturated/trans fat, cholesterol.
FH: Consider PCSK9i combined w/ statin to ↓LDL-C. If homozygous FH doesn’t respond to PCSK9i: lomitapide and mipomerson, available via restricted distribution, may be useful. Unclear if PCSK9i is cost-effective in heterozygous FH pts.
AACE drug tx
• Statins preferred to lower LDL-C. Simvastatin 80 mg not recommended.
• ASCVD = ACS, MI hx, angina, coronary/other arterial revasc, stroke, TIA, atherosclerotic PAD (including aortic aneurysm)
• ↑blood glucose and/or ↑new-onset T2DM risk don’t outweigh statin benefit; DM risk is dose related, primarily occurs in MetS pts; may be less common w/ pravastatin, possibly pitavastatin. Rosuvastatin plasma levels may be higher in Asians.
• Statin alternatives. Ezetimibe can be used as mono-tx to lower LDL-C, apoB, esp if statin-intolerant. Don’t use PCSK9i as mono-tx except if statin intolerant. Unclear if PCSK9i is cost-effective in heterozygous FH or ASCVD pts.
• Combo tx. If LDL-C or non-HDL-C goals not met: Combine max-tolerated statin w/ ezetimibe, bile acid sequestrants (caution if ↑TG), bempedoic acid, or PCSK9i.
• Mixed dyslipidemia (↑LDL-C, ↑TG, ↓HDL-C): If high-dose mono-tx inadequate, may use combo, eg, statin + IPE, statin + niacin (but no clinical CV benefit from adding niacin if LDL-C already well controlled w/ statin), statin + fibrate, statin + bile acid sequestrant (caution if ↑TG), ezetimibe + fibrate, or ezetimibe + niacin.
• ↓HDL-C: If no other risk factors, don’t treat it. If additional risk factors, raise HDL-C to >40 mg/dL, at minimum (both sexes).
Lifestyle: 30min mod-intense physical activity 4-6x/wk (≥10min/session) + musc strengthen 2x/wk. Low-cal, low–saturated/trans fat, low-chol diet w/ 5+ fruit/veg servings/day, grains (mostly whole), fish, lean meat; high fiber, ~2 g/day plant stanols/sterols. Smoking cessation.
3 DHHS 2024. U.S. Department of Health and Human Services Panel for the Use of Antiretroviral Agents in Adults and Adolescents with HIV, American College of Cardiology, American Heart Association, and HIV Medicine Association. Recommendations for the Use of Statin Therapy as Primary Prevention of Atherosclerotic Cardiovascular Disease in People with HIV. Clinicalinfo.HIV.gov. February 27, 2024. Accessed June 25, 2024. Full-text PDF
Assess ASCVD risk (calc,1 risks,1 risk-enhancing factors1) to inform shared decision-making on risk-reduction net benefits & pt preferences. AACE specifies target LDL-C based on risk.2 Heart-healthy lifestyle.2 Base decisions on 10-yr ASCVD risk, per ACC/AHA:1 - If <5% (low risk): lifestyle
- 5% to 7.4% (borderline): Presence of risk enhancers1 favor mod-intensity statins. If statin decision uncertain, consider CAC1 in select pts (eg, 40-55 yo)
- 7.5% to 19.9% (intermediate) w/ LDL-C 70-189: Mod-intensity statin, if discussion of risks and risk-enhancers1 (eg, CKD1) favors statins. For optimal risk reduction, esp if at higher risk,1 ↓LDL-C by ≥50%; if high-intensity not accepted/tolerated, mod-intensity statin plus add-on nonstatin (eg, ezetimibe, bile acid sequestrant) may be reasonable. If statin decision uncertain, consider CAC1
- ≥20% (high): statin to ↓ LDL-C by ≥50%
Select statin1 if indicated based on risk: For pts w/ HIV:3 - If <5% (low) ASCVD risk:
• Initiate at least moderate-intensity (30%-49% LDL-C–lowering) statin tx [CI]:
◦ pitavastatin 4 mg qd [AI]
◦ atorvastatin 20 mg qd [AII]
◦ rosuvastatin 10 mg qd [AII]
• Absolute benefit is modest, so decision to initiate statin should account for presence or absence of HIV-related factors that can ↑ ASCVD risk. Such factors include:
◦ prolonged HIV infection duration
◦ delayed ART initiation
◦ long periods of HIV viremia or tx nonadherence
◦ low current or nadir CD4 lymphocyte cell count (e.g., <350 cells/mm3)
◦ exposure to older ART drugs assoc w/ cardiometabolic toxicity
◦ hep C coinfection
• Atorvastatin and rosuvastatin interact w/ ritonavir- and cobicistat-boosted ARVs.
• If pregnant: Defer statin tx initiation until after pregnancy in pts at low to intermediate ASCVD risk. If on statin tx, discontinue. Breastfeeding is not recommended while on statin tx. - If 5% to <20% (intermediate) ASCVD risk:
• Initiate at least moderate-intensity (30%-49% LDL-C–lowering) statin tx [AI]:
◦ pitavastatin 4 mg qd [AI]
◦ atorvastatin 20 mg qd [AII]
◦ rosuvastatin 10 mg qd [AII]
• Atorvastatin and rosuvastatin interact w/ ritonavir- and cobicistat-boosted ARVs.
• If pregnant: Defer statin tx initiation until after pregnancy in pts at low to intermediate ASCVD risk. If on statin tx, discontinue. Breastfeeding is not recommended while on statin tx. - If ≥20% (high) ASCVD risk:
• Initiate high-intensity (≥50% LDL-C–lowering) statin tx:
◦ atorvastatin 40-80 mg qd
◦ rosuvastatin 20-40 mg qd
• Atorvastatin and rosuvastatin interact w/ ritonavir- and cobicistat-boosted ARVs.
• If pregnant: Defer statin tx initiation until after pregnancy in pts at low to intermediate ASCVD risk. If on statin tx, discontinue. Breastfeeding is not recommended while on statin tx.
Footnotes 1 2018 AHA/ACC/etc. Grundy SM, 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. J Am Coll Cardiol. 2019 June 25;73(24):3210-3227. Accessed 2/2/21
10-yr ASCVD risk calc based on pooled cohort equation. Best validated in non-Hispanic White/Black pts 40-75 yo.
High-risk conditions
• ≥65 yo
• Heterozygous FH
• CABG or PCI outside of major ASCVD event
• DM
• HTN
• CHF
• CKD (eGFR 15-59 mL/min/1.73m 2)
• Current smoker
• LDL-C persistently ≥100 despite max-tolerated statin + ezetimibe
Risk enhancers
• FHx of premature ASCVD
• Personal hx: CKD, preeclampsia, menopause <40 yo, metabolic syndrome (3 of these: ↑waist circ., TG >150 mg/dL, ↑BP, ↑glucose, HDL <40 men or <50 women), inflammatory dz (RA, psoriasis, chronic HIV), high-risk ethnicity (eg, South Asian)
• Labs. LDL-C persistently ≥160, TG persistently ≥175. If measured:
hs-CRP ≥2 mg/dL, Lp(a) ≥50 mg/dL, apoB ≥130 mg/dL
• ABI <0.9 (if measured)
Lifestyle. Wt loss prn. Exercise: Average of 40min mod-intense aerobic activity 3-4x/wk. Tobacco cessation. Diet: ↑vegetables, fruits, nuts, whole grains, legumes, lean veg/animal protein, fish. ↓trans fats, red/processed meat, refined carbs, sugar beverages.
Coronary Artery Calcium. Zero score can downgrade risk in some but doesn’t r/o risk from noncalcified plaque. CAC scoring might help pts reluctant to start/restart a statin, including 55- to 80-yo men and 60- to 80-yo women who have low risk factor burden; and pts 40-55 yo w/ 10-yr ASCVD risk 5% to 7.4% who have factors that ↑ their risk.
If CAC score is:
• 0. Withholding/delaying statins reasonable—except if cigarette smoker, DM, strong FHx of premature ASCVD, and possibly if chronic inflammatory conditions (eg, HIV)
• 1-99. Statins reasonable, esp if ≥55 yo
• ≥100 (or ≥75th percentile). Statins reasonable
CKD: Risk-enhancing factor for 40- to 75-yo pts w/ LDL-C 70-189 w/ 10-yr ASCVD risk ≥7.5%, if CKD isn’t treated w/ dialysis or kidney txp; starting mod-intensity statin or mod-intensity combo w/ ezetimibe can be useful/favored. In adults w/ advanced kidney dz on dialysis who are taking a statin, it may be reasonable to continue; however, it’s not recommended to start a statin.
2 2020 AACE/ACE. Handelsman Y, et al. Consensus Statement by the American Association of Clinical Endocrinologists and American College of Endocrinology on the Management of Dyslipidemia and Prevention of Cardiovascular Disease Algorithm – 2020 Executive Summary. Endocr Pract. 2020. Oct:26(10):1196-1224. Free full-text PDF
AACE risk groups
Extreme risk: Target LDL-C <55 mg/dL via statin (non-HDL-C <80, apoB <70); use high-dose statin therapy, or statins combo w/ ezetimibe/PCSK9i/colesevelam/bempedoic acid if target not achieved.
• progressive ASCVD (eg, unstable angina despite LDL-C <70)
• established clinical CVD in DM, CKD stage 3/4, or heterozygous FH
• personal hx premature ASCVD: <55-yo male, <65-yo female
Very high: Target LDL-C <70 mg/dL (may consider even lower) via statin (non-HDL-C <100, apoB <80); use high-dose statin therapy, or statins combo w/ ezetimibe/PCSK9i/colesevelam/bempedoic acid if target not achieved.
• ACS (established/recent hospitalization); coronary, carotid dz, PVD
• Framingham 10-yr risk >20%
• DM or CKD stage 3/4, plus 1+ additional risk factor(s)
• Heterozygous FH
High: Target LDL-C <100 mg/dL (may consider even lower) via statin (non-HDL-C <130, apoB <90); start mod-dose statin therapy; if target not achieved, then high-dose statin, followed by statins combo w/ ezetimibe/colesevelam/bempedoic acid; consider PCSK9i as last resort.
• 2+ risk factors w/ Framingham 10-yr risk 10% to 20%
• ASCVD equivalent including DM or CKD stage 3/4, w/o other risk factors
Mod: Target LDL-C <100 mg/dL recommended (non-HDL-C <130, apoB <90); start mod-dose statin therapy; if target not achieved, then high-dose statin, followed by statins combo w/ ezetimibe/colesevelam/bempedoic acid; consider PCSK9i as last resort.
• ≤2 risk factors w/ Framingham 10-yr risk <10%
Low: Target LDL-C <130 mg/dL recommended (non-HDL-C <160); start lifestyle; if target not achieved, use mod-dose statin therapy, then high-dose statin, followed by statins combo w/ ezetimibe/colesevelam/bempedoic acid.
• 0 risk factors
AACE risk factors: If HDL-C >60 mg/dL, subtract 1 risk factor.
• Major risk: advancing age, ↑total/non-HDL-C/LDL-C, ↓HDL, DM, HTN, CKD, cigarette smoking, FHx ASCVD (eg, MI/SCD <55-yo male 1st-deg relative or <65-yo female 1st-deg relative)
• Additional: obesity/abdominal obesity, FHx ↑lipids, ↑small dense LDL-C, ↑apoB, ↑LDL particle concentration, fasting/postprandial ↑TG, PCOS, dyslipidemia triad (↑TG + ↓HDL + ↑small dense LDL-C)
• Nontraditional: ↑Lp(a), ↑clotting factors, ↑inflammatory markers (hs-CRP, Lp-PLA2), ↑homocysteine, ↑uric acid, ↑TG-rich remnants
Considerations in women
• Women at high risk (eg, Framingham or Reynolds 10-yr risk >20%): lipid-lowering (preferably statin) regardless of LDL-C; if ↓HDL-C or ↑non-HDL-C, add niacin or fibrate. Diet low in saturated/trans fat, <200 mg/day cholesterol.
• Women at intermediate risk (eg, Framingham 10-yr risk 10%-20%): lipid-lowering (preferably statin) if LDL-C >130. Once LDL-C goal is reached, if ↓HDL-C or ↑non-HDL-C, add niacin or fibrate and diet low in saturated/trans fat, cholesterol.
• Postmenopausal women: Don’t use HRT for dyslipidemia.
FH: Consider PCSK9i combined w/ statin to ↓LDL-C. If homozygous FH doesn’t respond to PCSK9i: lomitapide and mipomerson, available via restricted distribution, may be useful. Unclear if PCSK9i is cost-effective in heterozygous FH pts.
AACE drug tx
• Statins preferred to lower LDL-C. Simvastatin 80 mg not recommended.
• ASCVD = ACS, MI hx, angina, coronary/other arterial revasc, stroke, TIA, atherosclerotic PAD (including aortic aneurysm)
• ↑blood glucose and/or ↑new-onset T2DM risk don’t outweigh statin benefit; DM risk is dose related, primarily occurs in MetS pts; may be less common w/ pravastatin, possibly pitavastatin. Rosuvastatin plasma levels may be higher in Asians.
• Statin alternatives. Ezetimibe can be used as mono-tx to lower LDL-C, apoB, esp if statin-intolerant. Don’t use PCSK9i as mono-tx except if statin intolerant. Unclear if PCSK9i is cost-effective in heterozygous FH or ASCVD pts.
• Combo tx. If LDL-C or non-HDL-C goals not met: Combine max-tolerated statin w/ ezetimibe, bile acid sequestrants (caution if ↑TG), bempedoic acid, or PCSK9i.
• Mixed dyslipidemia (↑LDL-C, ↑TG, ↓HDL-C): If high-dose mono-tx inadequate, may use combo, eg, statin + IPE, statin + niacin (but no clinical CV benefit from adding niacin if LDL-C already well controlled w/ statin), statin + fibrate, statin + bile acid sequestrant (caution if ↑TG), ezetimibe + fibrate, or ezetimibe + niacin.
• ↓HDL-C: If no other risk factors, don’t treat it. If additional risk factors, raise HDL-C to >40 mg/dL, at minimum (both sexes).
Lifestyle: 30min mod-intense physical activity 4-6x/wk (≥10min/session) + musc strengthen 2x/wk. Low-cal, low–saturated/trans fat, low-chol diet w/ 5+ fruit/veg servings/day, grains (mostly whole), fish, lean meat; high fiber, ~2 g/day plant stanols/sterols. Smoking cessation.
3 DHHS 2024. U.S. Department of Health and Human Services Panel for the Use of Antiretroviral Agents in Adults and Adolescents with HIV, American College of Cardiology, American Heart Association, and HIV Medicine Association. Recommendations for the Use of Statin Therapy as Primary Prevention of Atherosclerotic Cardiovascular Disease in People with HIV. Clinicalinfo.HIV.gov. February 27, 2024. Accessed June 25, 2024. Full-text PDF
Individualize shared decision-making for primary prevention in pts ≥75 yo, factoring ASCVD risk,1 health status, susceptibility to statin-related risks, & pt preference. AACE states that many older individuals benefit from lipid lowering.2 Heart-healthy lifestyle.1,2 Per ACC/AHA: - If LDL-C 70-189: After discussion, may be reasonable to start mod-intensity statin, though data limited; if 76-80 yo, may be reasonable to measure CAC,1 since zero CAC score could avoid statin for some
- Stopping statin reasonable when risks/adverse effects outweigh meaningful benefit, d/t physical/cognitive decline, life expectancy, etc
Select drug, if statin1 favored: - Mod-intensity (30%-49% LDL-C lowering): atorvastatin 10 or 20 mg, rosuvastatin 5 or 10 mg, simvastatin 20-40 mg, pravastatin 40 or 80 mg, lovastatin 40 or 80 mg, fluvastatin XL 80 mg, fluvastatin 40 mg bid, pitavastatin 1-4 mg
- Low-intensity (<30% LDL-C lowering): simvastatin 10 mg, pravastatin 10-20 mg, lovastatin 20 mg, fluvastatin 20-40 mg
Footnotes 1 2018 AHA/ACC/etc. Grundy SM, 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. J Am Coll Cardiol. 2019 June 25;73(24):3210-3227. Accessed 2/2/21
High-risk conditions
• ≥65 yo
• Heterozygous FH
• CABG or PCI outside of major ASCVD event
• DM
• HTN
• CHF
• CKD (eGFR 15-59 mL/min/1.73m 2)
• Current smoker
• LDL-C persistently ≥100 despite max-tolerated statin + ezetimibe
Risk enhancers
• FHx of premature ASCVD
• Personal hx: CKD, preeclampsia, menopause <40 yo, metabolic syndrome (3 of these: ↑waist circ., TG >150 mg/dL, ↑BP, ↑glucose, HDL <40 men or <50 women), inflammatory dz (RA, psoriasis, chronic HIV), high-risk ethnicity (eg, South Asian)
• Labs. LDL-C persistently ≥160, TG persistently ≥175. If measured:
hs-CRP ≥2 mg/dL, Lp(a) ≥50 mg/dL, apoB ≥130 mg/dL
• ABI <0.9 (if measured)
Lifestyle. Wt loss prn. Exercise: Average of 40min mod-intense aerobic activity 3-4x/wk. Tobacco cessation. Diet: ↑vegetables, fruits, nuts, whole grains, legumes, lean veg/animal protein, fish. ↓trans fats, red/processed meat, refined carbs, sugar beverages.
Coronary Artery Calcium. Zero score can downgrade risk in some but doesn’t r/o risk from noncalcified plaque. CAC scoring might help pts reluctant to start/restart a statin, including 55- to 80-yo men and 60- to 80-yo women who have low risk factor burden; and pts 40-55 yo w/ 10-yr ASCVD risk 5% to 7.4% who have factors that ↑ their risk.
If CAC score is:
• 0. Withholding/delaying statins reasonable—except if cigarette smoker, DM, strong FHx of premature ASCVD, and possibly if chronic inflammatory conditions (eg, HIV)
• 1-99. Statins reasonable, esp if ≥55 yo
• ≥100 (or ≥75th percentile). Statins reasonable
2 2020 AACE/ACE. Handelsman Y, et al. Consensus Statement by the American Association of Clinical Endocrinologists and American College of Endocrinology on the Management of Dyslipidemia and Prevention of Cardiovascular Disease Algorithm – 2020 Executive Summary. Endocr Pract. 2020. Oct:26(10):1196-1224. Free full-text PDF
Lifestyle: 30min mod-intense physical activity 4-6x/wk (≥10min/session) + musc strengthen 2x/wk. Low-cal, low–saturated/trans fat, low-chol diet w/ 5+ fruit/veg servings/day, grains (mostly whole), fish, lean meat; high fiber, ~2 g/day plant stanols/sterols. Smoking cessation.
AACE drug tx
• Statins preferred to lower LDL-C. Simvastatin 80 mg not recommended.
• ASCVD = ACS, MI hx, angina, coronary/other arterial revasc, stroke, TIA, atherosclerotic PAD (including aortic aneurysm)
• ↑blood glucose and/or ↑new-onset T2DM risk don’t outweigh statin benefit; DM risk is dose related, primarily occurs in MetS pts; may be less common w/ pravastatin, possibly pitavastatin. Rosuvastatin plasma levels may be higher in Asians.
• Statin alternatives. Ezetimibe can be used as mono-tx to lower LDL-C, apoB, esp if statin-intolerant. Don’t use PCSK9i as mono-tx except if statin intolerant. Unclear if PCSK9i is cost-effective in heterozygous FH or ASCVD pts.
• Combo tx. If LDL-C or non-HDL-C goals not met: Combine max-tolerated statin w/ ezetimibe, bile acid sequestrants (caution if ↑TG), bempedoic acid, or PCSK9i.
• Mixed dyslipidemia (↑LDL-C, ↑TG, ↓HDL-C): If high-dose mono-tx inadequate, may use combo, eg, statin + IPE, statin + niacin (but no clinical CV benefit from adding niacin if LDL-C already well controlled w/ statin), statin + fibrate, statin + bile acid sequestrant (caution if ↑TG), ezetimibe + fibrate, or ezetimibe + niacin.
• ↓HDL-C: If no other risk factors, don’t treat it. If additional risk factors, raise HDL-C to >40 mg/dL, at minimum (both sexes).
Considerations in women
• Women at high risk (eg, Framingham or Reynolds 10-yr risk >20%): lipid-lowering (preferably statin) regardless of LDL-C; if ↓HDL-C or ↑non-HDL-C, add niacin or fibrate. Diet low in saturated/trans fat, <200 mg/day cholesterol.
• Women at intermediate risk (eg, Framingham 10-yr risk 10%-20%): lipid-lowering (preferably statin) if LDL-C >130. Once LDL-C goal is reached, if ↓HDL-C or ↑non-HDL-C, add niacin or fibrate and diet low in saturated/trans fat, cholesterol.
• Postmenopausal women: Don’t use HRT for dyslipidemia.
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