Diagnostic Considerations
When triglycerides are noted to be elevated, always check a fasting blood sugar and HbA1c to rule out uncontrolled diabetes—one of the most frequent causes of hypertriglyceridemia. Management of this condition may make medication to lower the triglycerides unnecessary or, at least, make it easier to normalize.
A diet high in refined carbohydrates can cause hypertriglyceridemia. Although cakes, candy, cookies, etc, are an obvious source, the quantity of liquid calories (nondiet soda, juice, alcohol) should also be determined.
In addition, consider conditions such as hypertriglyceridemia with elevations of very low-density lipoprotein (VLDL) with or without chylomicronemia, as well as mixed hyperlipidemia (type IIb hyperlipidemia) with elevations of both low-density lipoprotein (LDL) and VLDL. Note that use of oral contraceptives, beta-blockers, and thiazide diuretics can also raise plasma triglyceride and VLDL levels.
First-degree relatives should be screened for hyperlipidemia.
Differential Diagnoses
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Alcohol Abuse
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Chylomicronemia
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Hormone Replacement Therapy
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Pancreatitis
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Renal Failure
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Eruptive xanthomas on the back of a patient admitted with a triglyceride level of 4600 mg/dL and acute pancreatitis.
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Close-up of eruptive xanthomas.
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Composition of triglyceride (TG)-rich lipoproteins. IDL = intermediate-density lipoprotein; VLDL = very low-density lipoprotein.
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Lipoprotein lipase (LPL) releases free fatty acids (FFAs) from chylomicrons (chylo) and produces chylomicron remnants that are small enough to take part in the atherosclerotic process. Chol = cholesterol; TGs, TGS = triglycerides.
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Once very low-density lipoprotein (VLDL) has been metabolized by lipoprotein lipase, VLDL remnants in the form of intermediate-density lipoprotein (IDL) can be metabolized by hepatic lipase, producing low-density lipoprotein (LDL), or they can be taken up by the LDL receptor via either apolipoprotein B (apo B) or apo E. Chol = cholesterol; TGs = triglycerides.
Tables
Type |
Serum Elevation |
Lipoprotein Elevation |
I |
Cholesterol and triglycerides |
Chylomicrons |
IIa |
Cholesterol |
LDL |
IIb |
Cholesterol and triglycerides |
LDL, VLDL |
III |
Cholesterol and triglycerides |
IDL |
IV |
Triglycerides |
VLDL |
V |
Cholesterol and triglycerides |
VLDL, chylomicrons |
IDL = intermediate-density lipoprotein; LDL = low-density lipoprotein; VLDL = very low-density lipoprotein. Source: Fredrickson DS, Lees RS. A system for phenotyping hyperlipidaemia. Circulation. Mar 1965;31:321-7. [3] |
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Classification |
TG level, mg/dL |
Normal triglyceride level |
< 150 |
Borderline-high triglyceride level |
150-199 |
High triglyceride level |
200-499 |
Very high triglyceride level |
>500 |
Source: National Cholesterol Education Program. Executive summary of the third report of The National Cholesterol Education Program (NCEP) Expert Panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III). JAMA. May 16 2001;285(19):2486-97. [14] |
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Classification |
LDL Goal, mg/dL |
Non-HDL Goal, mg/dL |
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CHD and CHD risk equivalent, diabetes mellitus, and the following: |
10-year risk for CHD >20% |
< 100 |
< 130 |
Two or more risk factors and the following: |
10-year risk < 20% |
< 130 |
< 160 |
0-1 risk factor |
< 160 |
< 190 |
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CHD = coronary heart disease; LDL = low-density lipoprotein; HDL = high-density lipoprotein. Source: National Cholesterol Education Program. Executive summary of the third report of The National Cholesterol Education Program (NCEP) Expert Panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III). JAMA. May 16 2001;285(19):2486-97. [14] |
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Drug |
Lipid Effects |
Lipid Effects in Combination with Statin |
Outcomes Data |
Comments |
Bezafibrate |
LDL decrease: 9.6-25% (400 mg) HDL increase: 15-24% (400 mg) Triglyceride decrease: 25-43% (400 mg) |
Further LDL decrease: 1.1% (400 mg) Further HDL increase: 22% (400 mg) Further triglyceride decrease: 31.7% (400 mg) |
Secondary prevention: Prevents composite endpoint of MI and sudden death in a subgroup with triglycerides of 200 mg/dL or higher. No increase in non-CV death |
First-line option for triglyceride >10 mmol/L Option for triglyceride 5-10 mmol/L Option for low HDL Reversible increase in serum creatinine Requires renal dose adjustment Limited data with statins |
Ezetimibe |
LDL decrease: 18% (10 mg/day) HDL increase: 1% (10 mg/day) Triglyceride decrease: 8% |
Further LDL decrease: 25%, as add-on Further HDL increase: 3%, as add-on Further triglyceride decrease: 14%, as add-on |
Prevention of CV events in post-acute coronary syndrome patient when added to statin showed a benefit of reducing the primary endpoint (composite of CV death, MI, unstable angina requiring rehospitalization, coronary revascularization or stroke) by 6.4% vs statin alone In intermediate outcomes studies, ezetimibe did not reduce regression of carotid intima-media thickness (surrogate marker) when added to a statin |
Efficacy studied in combination with atorvastatin, fluvastatin, lovastatin, pravastatin, and simvastatin Role as statin add-on to reduce LDL if HDL and triglyceride satisfactory |
Fenofibrate |
LDL decrease: 20.6% (145 mg) HDL increase: 11% (145 mg) Triglyceride decrease: 23.5-50.6% (greatest drop in patients with highest triglycerides) (145 mg) |
Further LDL decrease: 0-6% (200 mg) Further HDL increase: 13-17% (200 mg) Further triglyceride decrease: 20-32% (200 mg) |
Prevention of CV events in type 2 diabetes: Did not reduce primary composite outcome (nonfatal MI or CV death). Improved outcomes included nonfatal MI (24% decrease), coronary revascularization (21% decrease), progression to albuminuria, and reduced laser treatments for retinopathy. Nonsignificant increase in risk of CV death. |
First-line option for triglyceride >10 mmol/L (about 1000 mg/dL) Option for triglyceride >500 mg/dL or 5-10 mmol/L Option for low HDL Requires renal dose adjustment Associated with reversible increase in serum creatinine |
Gemfibrozil |
LDL: No effect HDL increase: 6% (1200 mg/day) Triglyceride decrease: 33-50% (greatest drop in patients with highest triglycerides) (1200 mg/day) |
Further triglyceride decrease: 41% Further HDL increase: 9% |
Primary prevention of coronary heart disease Secondary prevention of cardiac events in men with low HDL |
First-line option for triglyceride >10 mmol/L (about 1000 mg/dL) Option for triglyceride >500 mg/dL or 5-10 mmol/L Option for low HDL Requires renal dose adjustment Avoid with statin |
Icosapent ethyl |
LDL decrease: 5% HDL decrease: 4% Triglyceride decrease: 27% |
Further triglyceride decrease: 21.5% (4 g/day), 10.1% (2 g/day) Further LDL decrease: 6.2% (4 g/day) |
Secondary CV risk prevention; REDUCE-IT trial showed primary endpoint (major CV events) occurred in 24.7% of placebo compared with 18.2% of icosapent ethyl treated patients (p = 0.000001) [80] |
Option for triglyceride >500 mg/dL Safe for use with statins Use caution with fish or shellfish allergy |
Niacin |
LDL decrease: 14-17% (Niaspan 2 g/day); 12% (niacin immediate-release 1.5 g/day and Niaspan 1.5 g/day) HDL increase: 22-26% (2 g/day Niaspan); 17% (niacin immediate release 1.5 g/day); 20-22% (Niaspan 1.5 g/day) Triglyceride decrease: 20-50% |
Further LDL decrease: 1-5% (Niaspan 1 g/day); 10% (Niaspan 2 g/day) Further HDL increase: 24% (Niaspan 2 g/day); 15-17% (Niaspan 1 g/day) Further triglyceride decrease: 24% (Niaspan 2 g/day); 12-22% (Niaspan 1 g/day) |
Secondary MI prevention; in combination with a resin, slows progression or promotes regression of atherosclerosis; reduces mortality |
Option for triglyceride >500 mg/dL (about 5 mmol/L) Raises HDL more than any other agent Dose-dependent risk of hyperglycemia (especially in patients with type 2 diabetes) and liver toxicity May increase risk of statin myopathy |
Omega-3 ethyl esters |
LDL increase: 44.5% (4 g/day) HDL increase: 9.1% (4 g/day) Triglyceride decrease: 45% (4 g/day) |
LDL increase: 0.7% (4 g/day) Further HDL increase: 3.4% (4 g/day) Further triglyceride decrease: 29.5% (4 g/day) |
Secondary prevention: Reduces cardiovascular death; sudden death; and combined endpoint of death, nonfatal MI, and nonfatal stroke Secondary prevention in patients with, or at risk for, type 2 diabetes: did not reduce CV events |
Option for triglyceride >500 mg/dL (about 5 mmol/L) Safe for use with statins Associated with an increase in risk for recurrence of symptomatic atrial fibrillation or flutter within first 3 months of therapy Use with caution with fish or shellfish allergy |
Drug |
Potency (average LDL decrease) |
Renal Considerations |
Liver Function Monitoring |
Atorvastatin |
10 mg: 35-39% 20 mg: 43% 40 mg: 50% 80 mg: 55-60% |
No dose adjustment necessary for reduced renal function |
Check liver function tests at baseline and when clinically indicated |
Fluvastatin |
20 mg: 22% 40 mg: 25% 80 mg: 35% (as XL product) |
In severe renal impairment, use daily doses >40 mg with caution |
Check liver function tests at baseline and when clinically indicated |
Lovastatin |
10 mg: 21% 20 mg: 24-27% 40 mg: 30-31% 80 mg: 40-42% (as 40 mg BID) |
If CrCl < 30 mL/min, use daily doses over 20 mg with caution |
Check liver function tests at baseline and when clinically indicated |
Pitavastatin |
1 mg: 31-32% 2 mg: 36-39% 4 mg: 41-45% |
For glomerular filtration rate 15-59 mL/min/1.73 m2, including hemodialysis, initial daily dose is 1 mg, not to exceed 2 mg/day |
Check liver function tests at baseline and when clinically indicated |
Pravastatin |
10 mg: 22% 20 mg: 32% 40 mg: 34% 80 mg: 37% |
In significant renal impairment, start with 10 mg/day |
Check liver function tests at baseline and when clinically indicated |
Rosuvastatin |
5 mg: 45% 10 mg: 46-52% 20 mg: 47-55% 40 mg: 55-63% |
If CrCl < 30 mL/min/1.73 m2 (but not on hemodialysis), starting dose is 5 mg/day, not exceed 10 mg/day Rosuvastatin levels in hemodialysis patients are about 50% higher than levels in normal renal function |
Check liver function tests at baseline and when clinically indicated |
Simvastatin |
5 mg: 26% 10 mg: 30% 20 mg: 38% 40 mg: 29-41% 80 mg: 36-47% |
In severe renal impairment, starting dose is 5 mg daily with close monitoring |
Check liver function tests at baseline and when clinically indicated |
