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1.
Low density lipoprotein (LDL) cholesterol was the primary lipid treatment target for most CVD outcomes trials, and LDL cholesterol is the primary lipid treatment target according to most lipid guidelines [50,51]. However, compared to low density lipoprotein (LDL) cholesterol, apolipoprotein B, non-high density lipoprotein (non-HDL) cholesterol and LDL particle number may be better predictors of CVD risk for many patients with dyslipidemia, such as patients having hypertriglyceridemia, non-fasting blood samples, and those with very low LDL cholesterol levels [[52], [53], [54]].
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2.
Treatment terminology differs among cholesterol guidelines, often with lipid treatment “targets” being the lipid parameter being treated (e.g., LDL-cholesterol), lipid “goals” being the desired lipid parameter level, and “threshold” being the level by which if exceeded, may prompt the addition or intensification of lipid-pharmacotherapy (e.g., LDL cholesterol ≥ 70 for patients at very high CVD risk or ≥100 mg/dL for patients at high CVD risk) [50,51].
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3.
In most cases, elevated triglyceride (TG) levels are a risk factor for CVD, especially if the elevated TG levels represent an increase in atherogenic triglyceride-rich lipoproteins (e.g., very-low-density lipoproteins, intermediate density lipoproteins, remnant lipoproteins) [55].
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4.
Lipoprotein (a) is an LDL-like particle attached to apolipoprotein (a), which is thought to be atherogenic, possibly thrombogenic, and is a CVD risk factor. It is uncertain that lowering Lp(a) alone reduces CVD risk. Statins do not lower Lp(a); PCSK9 inhibitors lower Lp(a) [56,57].
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5.
Heterozygous Familial Hypercholesterolemia (HeFH) is the most common genetic disorder resulting in severe elevations in LDL-cholesterol (i.e., typically with LDL-cholesterol levels ≥ 190 mg/dL), with a reported prevalence of 1/200 to 1/500. Patients with FH are at high risk for premature CVD. Management of HeFH includes aggressive cholesterol lowering at an early age, usually involving statin therapy [58].
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6.
Statins are the most recommended drug treatment for hypercholesterolemia due to their cholesterol-lowering efficacy, safety, and CVD benefits supported by multiple cardiovascular outcomes trials [4]. In appropriate patients, “high intensity statins” (atorvastatin 40–80 mg or rosuvastatin 20–40 mg) may lower LDL cholesterol ≥ 50%, and are often recommended as first-line therapy in patients with CVD or at high risk for CVD [50,51]. Statin intolerance (e.g., statin-associated muscle symptoms or SAMS) may limit the dose or use of statins [59,60].
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7.
Ezetimibe modestly lowers LDL cholesterol levels ~18% and may modestly reduce CVD risk [61]. Bempedoic acid lowers LDL cholesterol ~ 20%, and when combined with ezetimibe in a fixed dose combination, lowers LDL cholesterol ~ 40%. A CVD outcome study with bempedoic acid is ongoing [62,63].
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8.
PCSK9 inhibitors are injectable agents that lower LDL cholesterol ≥50% and reduce CVD risk when added to high intensity or maximally tolerated statins [50,51].
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9.
Omega-3 fatty acids lower triglycerides and non-HDL cholesterol. Prescription icosapent ethyl is an eicosapentaenoic acid, ethyl ester agent that in a CVD outcomes trial, reduced the risk of CVD in patients at high CVD risk having triglyceride levels ≥150 mg/dL [64].
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10.
Fibrates are clinically used to lower triglyceride levels. However, no cardiovascular outcome study has yet reported that, as a primary endpoint, fibrates reduce CVD risk in patients specifically enrolled with high triglycerides. Post hoc analyses support that fibrates are most likely to reduce CVD in patients with baseline high triglycerides (and lower HDL cholesterol) [65].
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